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Asthma exacerbation in pregnancy impacts mothers, infants
Women with asthma who suffer asthma exacerbation while pregnant are at increased risk for complications during pregnancy and delivery, and their infants are at increased risk for respiratory problems, according to data from a longitudinal study of 58,524 women with asthma.
“Asthma exacerbation during pregnancy has been found to be associated with adverse perinatal and pregnancy outcomes such as low birth weight, small for gestational age, preterm delivery, congenital malformation, preeclampsia, and perinatal mortality,” but previous studies have been small and limited to comparisons of asthmatic and nonasthmatic women, wrote Kawsari Abdullah, PhD, of Children’s Hospital of Eastern Ontario, Ottawa, and colleagues.
To determine the impact of asthma exacerbation on maternal and fetal outcomes, the researchers analyzed data from the Ontario Asthma Surveillance Information System to identify women with asthma who had at least one pregnancy resulting in a live or still birth between 2006 and 2012.
Overall, significantly more women with exacerbated asthma had preeclampsia or pregnancy-induced hypertension, compared with asthmatic women who had no exacerbations, at 5% vs. 4% and 7% vs. 5%, respectively (P less than .001), according to the study published in the European Respiratory Journal.
Adverse perinatal outcomes were significantly more likely among babies of mothers with exacerbated asthma, compared with those who had no exacerbations, including low birth weight (7% vs. 5%), small for gestational age (3% vs. 2%), preterm birth (8% vs. 7%), and congenital malformation (6% vs. 5%). All P values were less than .001, except for small for gestational age, which was P = .008.
In addition, significantly more babies of asthmatic women with exacerbated asthma during pregnancy had respiratory problems including asthma and pneumonia, compared with those of asthmatic women who had no exacerbations during pregnancy, at 38% vs. 31% and 24% vs. 22% (P less than .001 for both). The researchers found no significant interactions between maternal age and smoking and asthma exacerbations.
The findings were limited by several factors, including the lack of a validated algorithm for asthma exacerbation, which the researchers defined as five or more visits to a general practice clinician for asthma during pregnancy. Other limitations included the lack of categorizing asthma exacerbation by severity, and the inability to include the potential effects of asthma medication on maternal and fetal outcomes, Dr. Abdullah and colleagues noted.
However, the results were strengthened by the large sample size and ability to follow babies from birth until 5 years of age, they said.
“Targeting women with asthma during pregnancy and ensuring appropriate asthma management and postpartum follow-up may help to reduce the risk of pregnancy complications, adverse perinatal outcomes, and early childhood respiratory disorders,” they concluded.
This study is important because asthma is a common, potentially serious medical condition that complicates approximately 4%-8% of pregnancies, and one in three women with asthma experience an exacerbation during pregnancy, Iris Krishna, MD, a specialist in maternal/fetal medicine at Emory University, Atlanta, said in an interview.
“This study is unique in that it uses population-level data to assess the association between an asthma exacerbation during pregnancy and adverse perinatal outcomes,” Dr. Krishna said. “After adjusting for confounders, and consistent with previous studies, study findings suggest an increased risk for women with asthma who have an asthma exacerbation during pregnancy for preeclampsia [odds ratio, 1.3; P less than .001], pregnancy-induced hypertension [OR, 1.17; P less than .05], low-birth-weight infant [OR, 1.14; P less than .05], preterm birth [OR, 1.14; P less than .05], and congenital malformations [OR, 1.21; P less than .001].”
Dr. Krishna also noted the impact on early childhood outcomes. “In this study, children born to women who had an asthma exacerbation during pregnancy had a 23% higher risk of developing asthma before 5 years of age, which is consistent with previous studies. [The] investigators also reported a 12% higher risk of having pneumonia during the first 5 years of life for children born to women who had an asthma exacerbation during pregnancy.”
“Previous studies have suggested children born to mothers with uncontrolled asthma have an increased risk for respiratory infections, but this study is the first to report an association with pneumonia,” she said. This increased risk for childhood respiratory disorders warrants further study.
Consequently, “Women with asthma during pregnancy should have appropriate management to ensure good control to optimize pregnancy outcome,” Dr. Krishna emphasized. “Women who experience asthma exacerbations in pregnancy are at increased risk for preeclampsia, [pregnancy-induced hypertension], low birth weight, and preterm delivery and may require closer monitoring.”
The study was supported by the Institute for Clinical Evaluative Sciences. The researchers and Dr. Krishna had no financial conflicts to disclose.
SOURCE: Abdullah K et al. Eur Respir J. 2019 Nov 26. doi: 10.1183/13993003.01335-2019.
Women with asthma who suffer asthma exacerbation while pregnant are at increased risk for complications during pregnancy and delivery, and their infants are at increased risk for respiratory problems, according to data from a longitudinal study of 58,524 women with asthma.
“Asthma exacerbation during pregnancy has been found to be associated with adverse perinatal and pregnancy outcomes such as low birth weight, small for gestational age, preterm delivery, congenital malformation, preeclampsia, and perinatal mortality,” but previous studies have been small and limited to comparisons of asthmatic and nonasthmatic women, wrote Kawsari Abdullah, PhD, of Children’s Hospital of Eastern Ontario, Ottawa, and colleagues.
To determine the impact of asthma exacerbation on maternal and fetal outcomes, the researchers analyzed data from the Ontario Asthma Surveillance Information System to identify women with asthma who had at least one pregnancy resulting in a live or still birth between 2006 and 2012.
Overall, significantly more women with exacerbated asthma had preeclampsia or pregnancy-induced hypertension, compared with asthmatic women who had no exacerbations, at 5% vs. 4% and 7% vs. 5%, respectively (P less than .001), according to the study published in the European Respiratory Journal.
Adverse perinatal outcomes were significantly more likely among babies of mothers with exacerbated asthma, compared with those who had no exacerbations, including low birth weight (7% vs. 5%), small for gestational age (3% vs. 2%), preterm birth (8% vs. 7%), and congenital malformation (6% vs. 5%). All P values were less than .001, except for small for gestational age, which was P = .008.
In addition, significantly more babies of asthmatic women with exacerbated asthma during pregnancy had respiratory problems including asthma and pneumonia, compared with those of asthmatic women who had no exacerbations during pregnancy, at 38% vs. 31% and 24% vs. 22% (P less than .001 for both). The researchers found no significant interactions between maternal age and smoking and asthma exacerbations.
The findings were limited by several factors, including the lack of a validated algorithm for asthma exacerbation, which the researchers defined as five or more visits to a general practice clinician for asthma during pregnancy. Other limitations included the lack of categorizing asthma exacerbation by severity, and the inability to include the potential effects of asthma medication on maternal and fetal outcomes, Dr. Abdullah and colleagues noted.
However, the results were strengthened by the large sample size and ability to follow babies from birth until 5 years of age, they said.
“Targeting women with asthma during pregnancy and ensuring appropriate asthma management and postpartum follow-up may help to reduce the risk of pregnancy complications, adverse perinatal outcomes, and early childhood respiratory disorders,” they concluded.
This study is important because asthma is a common, potentially serious medical condition that complicates approximately 4%-8% of pregnancies, and one in three women with asthma experience an exacerbation during pregnancy, Iris Krishna, MD, a specialist in maternal/fetal medicine at Emory University, Atlanta, said in an interview.
“This study is unique in that it uses population-level data to assess the association between an asthma exacerbation during pregnancy and adverse perinatal outcomes,” Dr. Krishna said. “After adjusting for confounders, and consistent with previous studies, study findings suggest an increased risk for women with asthma who have an asthma exacerbation during pregnancy for preeclampsia [odds ratio, 1.3; P less than .001], pregnancy-induced hypertension [OR, 1.17; P less than .05], low-birth-weight infant [OR, 1.14; P less than .05], preterm birth [OR, 1.14; P less than .05], and congenital malformations [OR, 1.21; P less than .001].”
Dr. Krishna also noted the impact on early childhood outcomes. “In this study, children born to women who had an asthma exacerbation during pregnancy had a 23% higher risk of developing asthma before 5 years of age, which is consistent with previous studies. [The] investigators also reported a 12% higher risk of having pneumonia during the first 5 years of life for children born to women who had an asthma exacerbation during pregnancy.”
“Previous studies have suggested children born to mothers with uncontrolled asthma have an increased risk for respiratory infections, but this study is the first to report an association with pneumonia,” she said. This increased risk for childhood respiratory disorders warrants further study.
Consequently, “Women with asthma during pregnancy should have appropriate management to ensure good control to optimize pregnancy outcome,” Dr. Krishna emphasized. “Women who experience asthma exacerbations in pregnancy are at increased risk for preeclampsia, [pregnancy-induced hypertension], low birth weight, and preterm delivery and may require closer monitoring.”
The study was supported by the Institute for Clinical Evaluative Sciences. The researchers and Dr. Krishna had no financial conflicts to disclose.
SOURCE: Abdullah K et al. Eur Respir J. 2019 Nov 26. doi: 10.1183/13993003.01335-2019.
Women with asthma who suffer asthma exacerbation while pregnant are at increased risk for complications during pregnancy and delivery, and their infants are at increased risk for respiratory problems, according to data from a longitudinal study of 58,524 women with asthma.
“Asthma exacerbation during pregnancy has been found to be associated with adverse perinatal and pregnancy outcomes such as low birth weight, small for gestational age, preterm delivery, congenital malformation, preeclampsia, and perinatal mortality,” but previous studies have been small and limited to comparisons of asthmatic and nonasthmatic women, wrote Kawsari Abdullah, PhD, of Children’s Hospital of Eastern Ontario, Ottawa, and colleagues.
To determine the impact of asthma exacerbation on maternal and fetal outcomes, the researchers analyzed data from the Ontario Asthma Surveillance Information System to identify women with asthma who had at least one pregnancy resulting in a live or still birth between 2006 and 2012.
Overall, significantly more women with exacerbated asthma had preeclampsia or pregnancy-induced hypertension, compared with asthmatic women who had no exacerbations, at 5% vs. 4% and 7% vs. 5%, respectively (P less than .001), according to the study published in the European Respiratory Journal.
Adverse perinatal outcomes were significantly more likely among babies of mothers with exacerbated asthma, compared with those who had no exacerbations, including low birth weight (7% vs. 5%), small for gestational age (3% vs. 2%), preterm birth (8% vs. 7%), and congenital malformation (6% vs. 5%). All P values were less than .001, except for small for gestational age, which was P = .008.
In addition, significantly more babies of asthmatic women with exacerbated asthma during pregnancy had respiratory problems including asthma and pneumonia, compared with those of asthmatic women who had no exacerbations during pregnancy, at 38% vs. 31% and 24% vs. 22% (P less than .001 for both). The researchers found no significant interactions between maternal age and smoking and asthma exacerbations.
The findings were limited by several factors, including the lack of a validated algorithm for asthma exacerbation, which the researchers defined as five or more visits to a general practice clinician for asthma during pregnancy. Other limitations included the lack of categorizing asthma exacerbation by severity, and the inability to include the potential effects of asthma medication on maternal and fetal outcomes, Dr. Abdullah and colleagues noted.
However, the results were strengthened by the large sample size and ability to follow babies from birth until 5 years of age, they said.
“Targeting women with asthma during pregnancy and ensuring appropriate asthma management and postpartum follow-up may help to reduce the risk of pregnancy complications, adverse perinatal outcomes, and early childhood respiratory disorders,” they concluded.
This study is important because asthma is a common, potentially serious medical condition that complicates approximately 4%-8% of pregnancies, and one in three women with asthma experience an exacerbation during pregnancy, Iris Krishna, MD, a specialist in maternal/fetal medicine at Emory University, Atlanta, said in an interview.
“This study is unique in that it uses population-level data to assess the association between an asthma exacerbation during pregnancy and adverse perinatal outcomes,” Dr. Krishna said. “After adjusting for confounders, and consistent with previous studies, study findings suggest an increased risk for women with asthma who have an asthma exacerbation during pregnancy for preeclampsia [odds ratio, 1.3; P less than .001], pregnancy-induced hypertension [OR, 1.17; P less than .05], low-birth-weight infant [OR, 1.14; P less than .05], preterm birth [OR, 1.14; P less than .05], and congenital malformations [OR, 1.21; P less than .001].”
Dr. Krishna also noted the impact on early childhood outcomes. “In this study, children born to women who had an asthma exacerbation during pregnancy had a 23% higher risk of developing asthma before 5 years of age, which is consistent with previous studies. [The] investigators also reported a 12% higher risk of having pneumonia during the first 5 years of life for children born to women who had an asthma exacerbation during pregnancy.”
“Previous studies have suggested children born to mothers with uncontrolled asthma have an increased risk for respiratory infections, but this study is the first to report an association with pneumonia,” she said. This increased risk for childhood respiratory disorders warrants further study.
Consequently, “Women with asthma during pregnancy should have appropriate management to ensure good control to optimize pregnancy outcome,” Dr. Krishna emphasized. “Women who experience asthma exacerbations in pregnancy are at increased risk for preeclampsia, [pregnancy-induced hypertension], low birth weight, and preterm delivery and may require closer monitoring.”
The study was supported by the Institute for Clinical Evaluative Sciences. The researchers and Dr. Krishna had no financial conflicts to disclose.
SOURCE: Abdullah K et al. Eur Respir J. 2019 Nov 26. doi: 10.1183/13993003.01335-2019.
FROM THE EUROPEAN RESPIRATORY JOURNAL
Do women with diabetes need more CVD risk reduction than men?
BUSAN, SOUTH KOREA – Whether cardiovascular disease risk reduction efforts should be more aggressive in women than men with diabetes depends on how you interpret the data.
Two experts came to different conclusions on this question during a heated, but jovial, debate last week here at the International Diabetes Federation 2019 Congress.
Endocrinologist David Simmons, MB, BChir, Western Sydney University, Campbelltown, Australia, argued that diabetes erases the well-described life expectancy advantage of 4-7 years that women experience over men in the general population.
He also highlighted the fact that the heightened risk is of particular concern in both younger women and those with prior gestational diabetes.
But Timothy Davis, BMedSc, MB, BS, DPhil, an endocrinologist and general physician at Fremantle (Australia) Hospital, countered that the data only show the diabetes-attributable excess cardiovascular risk is higher in women than men, but that the absolute risk is actually greater in men.
Moreover, he argued, at least in type 1 diabetes, there is no evidence that more aggressive cardiovascular risk factor management improves outcomes.
Yes: Diabetes eliminates female CVD protection
Dr. Simmons began by pointing out that, although on average women die at an older age than men, it has been known for over 40 years that this “female protection” is lost in insulin-treated women, particularly as a result of their increased risk for cardiovascular disease.
In a 2015 meta-analysis of 26 studies, women with type 1 diabetes were found to have about a 37% greater risk of all-cause mortality, compared with men with the condition when mortality is contrasted with that of the general population, and twice the risk of both fatal and nonfatal vascular events.
The risk appeared to be greater in women who were younger at the time of diabetes diagnosis. “This is a really important point – the time we would want to intervene,” Dr. Simmons said.
In another meta-analysis of 30 studies including 2,307,694 individuals with type 2 diabetes and 252,491 deaths, the pooled women-to-men ratio of the standardized mortality ratio for all-cause mortality was 1.14.
In those with versus without type 2 diabetes, the pooled standardized mortality ratio in women was 2.30 and in men was 1.94, both significant, compared with those without diabetes.
And in a 2006 meta-analysis of 22 studies involving individuals with type 2 diabetes, the pooled data showed a 46% excess relative risk using standardized mortality ratios in women versus men for fatal coronary artery disease.
Meanwhile, in a 2018 meta-analysis of 68 studies involving nearly 1 million adults examining differences in occlusive vascular disease, after controlling for major vascular risk factors, diabetes roughly doubled the risk for occlusive vascular mortality in men (relative risk, 2.10), but tripled it in women (3.00).
Women with diabetes aged 35-59 years had the highest relative risk for death over follow-up across all age and sex groups: They had 5.5 times the excess risk, compared with those without diabetes, while the excess risk for men of that age was 2.3-fold.
“So very clearly, it’s these young women who are most at risk, “emphasized Dr. Simmons, who is an investigator for Novo Nordisk and a speaker for Medtronic, Novo Nordisk, and Sanofi.
Are disparities because of differences in cvd risk factor management?
The question has arisen whether the female/male differences might be because of differences in cardiovascular risk factor management, Simmons noted.
A 2015 American Heart Association statement laid out the evidence for lower prescribing of statins, aspirin, beta-blockers, and ACE inhibitors in women, compared with men, Dr. Simmons said.
And some studies suggest medication adherence is lower in women than men.
In terms of medications, fenofibrate appears to produce better outcomes in women than men, but there is no evidence of gender differences in the effects of statins, ACE inhibitors, or aspirin, Simmons said.
He also outlined the results of a 2008 study of 78,254 patients with acute myocardial infarction from 420 U.S. hospitals in 2001-2006.
Women were older, had more comorbidities, less often presented with ST-elevation myocardial infarction (STEMI), and had a higher rate of unadjusted in-hospital death (8.2% vs. 5.7%; P less than .0001) than men. Of the participants, 33% of women had diabetes, compared with 28% of men.
The in-hospital mortality difference disappeared after multivariable adjustment, but women with STEMI still had higher adjusted mortality rates than men.
“The underuse of evidence-based treatments and delayed reperfusion in women represent potential opportunities for reducing sex disparities in care and outcome after acute myocardial infarction,” the authors concluded.
“It’s very clear amongst our cardiology colleagues that something needs to be done and that we need more aggressive cardiological risk reduction in women,” Dr. Simmons said.
“The AHA has already decided this. It’s already a policy. So why are we having this debate?” he wondered.
He also pointed out that women with prior gestational diabetes are an exceptionally high–risk group, with a twofold excess risk for cardiovascular disease within the first 10 years post partum.
“We need to do something about this particularly high-risk group, independent of debates about gender,” Dr. Simmons emphasized. “Clearly, women with diabetes warrant more aggressive cardiovascular risk reduction than men with diabetes, especially at those younger ages,” he concluded.
No: Confusion about relative risk within each sex and absolute risk
Dr. Davis began his counterargument by stating that estimation of absolute vascular risk is an established part of strategies to prevent cardiovascular disease, including in diabetes.
And that risk, he stressed, is actually higher in men.
“Male sex is a consistent adverse risk factor in cardiovascular disease event prediction equations in type 2 diabetes. Identifying absolute risk is important,” he said, noting risk calculators include male sex, such as the risk engine derived from the United Kingdom Prospective Diabetes Trial.
And in the Australian population-based Fremantle study, of which Dr. Davis is an author, the absolute 5-year incidence rates for all outcomes – including myocardial infarction, stroke, heart failure, lower extremity amputation, cardiovascular mortality, and all-cause mortality – were consistently higher in men versus women in the first phase, which began in the 1990s and included 1,426 individuals with diabetes (91% had type 2 diabetes).
In the ongoing second phase, which began in 2008 with 1,732 participants, overall rates of those outcomes are lower and the discrepancy between men and women has narrowed, Dr. Davis noted.
Overall, the Fremantle study data “suggest that women with type 2 diabetes do not need more aggressive cardiovascular reduction than men with type 2 diabetes because they are not at increased absolute vascular risk,” he stressed.
And in a “sensitivity analysis” of two areas in Finland, the authors concluded that the stronger effect of type 2 diabetes on the risk of congenital heart disease (CHD) in women, compared with men was in part explained by a heavier risk factor burden and a greater effect of blood pressure and atherogenic dyslipidemia in women with diabetes, he explained.
The Finnish authors wrote, “In terms of absolute risk of CHD death or a major CHD event, diabetes almost completely abolished the female protection from CHD.”
But, Dr. Davis emphasized, rates were not higher in females.
So then, “why is there the view that women with type 2 diabetes need more aggressive cardiovascular risk reduction than men with diabetes?
“It probably comes back to confusion based on absolute risk versus a comparison of relative risk within each sex,” he asserted.
ADA Standards of Medical Care 2019 don’t mention gender
Lastly, in a meta-analysis published just in July this year involving more than 5 million participants, compared with men with diabetes, women with diabetes had a 58% and 13% greater risk of CHD and all-cause mortality, respectively.
“This points to an urgent need to develop sex- and gender-specific risk assessment strategies and therapeutic interventions that target diabetes management in the context of CHD prevention,” the authors concluded.
But, Dr. Davis noted, “It is not absolute vascular risk. It’s a relative risk compared across the two genders. In the paper, there is no mention of absolute vascular risk.
“Greater CVD mortality in women with and without diabetes, versus men, doesn’t mean there’s also an absolute vascular increase in women versus men with diabetes,” he said.
Moreover, Dr. Davis pointed out that in an editorial accompanying the 2015 meta-analysis in type 1 diabetes, Simmons had actually stated that absolute mortality rates are highest in men.
“I don’t know what happened to his epidemiology knowledge in the last 4 years but it seems to have gone backwards,” he joked to his debate opponent.
And, Dr. Davis asserted, even if there were a higher risk in women with type 1 diabetes, there is no evidence that cardiovascular risk reduction measures affect endpoints in that patient population. Only about 8% of people with diabetes in statin trials had type 1 diabetes.
Indeed, he noted, in the American Diabetes Association Standards of Medical Care in Diabetes – 2019, the treatment goals for individual cardiovascular risk factors do not mention gender.
What’s more, Dr. David said, there is evidence that women are significantly less likely than men to take prescribed statins and are more likely to have an eating disorder and underdose insulin, “suggesting significant issues with compliance. ... So, trying to get more intensive risk reduction in women may be a challenge.”
“Women with diabetes do not need more aggressive cardiovascular risk reduction than men with diabetes, irrespective of type,” he concluded.
A version of this story originally appeared on medscape.com.
BUSAN, SOUTH KOREA – Whether cardiovascular disease risk reduction efforts should be more aggressive in women than men with diabetes depends on how you interpret the data.
Two experts came to different conclusions on this question during a heated, but jovial, debate last week here at the International Diabetes Federation 2019 Congress.
Endocrinologist David Simmons, MB, BChir, Western Sydney University, Campbelltown, Australia, argued that diabetes erases the well-described life expectancy advantage of 4-7 years that women experience over men in the general population.
He also highlighted the fact that the heightened risk is of particular concern in both younger women and those with prior gestational diabetes.
But Timothy Davis, BMedSc, MB, BS, DPhil, an endocrinologist and general physician at Fremantle (Australia) Hospital, countered that the data only show the diabetes-attributable excess cardiovascular risk is higher in women than men, but that the absolute risk is actually greater in men.
Moreover, he argued, at least in type 1 diabetes, there is no evidence that more aggressive cardiovascular risk factor management improves outcomes.
Yes: Diabetes eliminates female CVD protection
Dr. Simmons began by pointing out that, although on average women die at an older age than men, it has been known for over 40 years that this “female protection” is lost in insulin-treated women, particularly as a result of their increased risk for cardiovascular disease.
In a 2015 meta-analysis of 26 studies, women with type 1 diabetes were found to have about a 37% greater risk of all-cause mortality, compared with men with the condition when mortality is contrasted with that of the general population, and twice the risk of both fatal and nonfatal vascular events.
The risk appeared to be greater in women who were younger at the time of diabetes diagnosis. “This is a really important point – the time we would want to intervene,” Dr. Simmons said.
In another meta-analysis of 30 studies including 2,307,694 individuals with type 2 diabetes and 252,491 deaths, the pooled women-to-men ratio of the standardized mortality ratio for all-cause mortality was 1.14.
In those with versus without type 2 diabetes, the pooled standardized mortality ratio in women was 2.30 and in men was 1.94, both significant, compared with those without diabetes.
And in a 2006 meta-analysis of 22 studies involving individuals with type 2 diabetes, the pooled data showed a 46% excess relative risk using standardized mortality ratios in women versus men for fatal coronary artery disease.
Meanwhile, in a 2018 meta-analysis of 68 studies involving nearly 1 million adults examining differences in occlusive vascular disease, after controlling for major vascular risk factors, diabetes roughly doubled the risk for occlusive vascular mortality in men (relative risk, 2.10), but tripled it in women (3.00).
Women with diabetes aged 35-59 years had the highest relative risk for death over follow-up across all age and sex groups: They had 5.5 times the excess risk, compared with those without diabetes, while the excess risk for men of that age was 2.3-fold.
“So very clearly, it’s these young women who are most at risk, “emphasized Dr. Simmons, who is an investigator for Novo Nordisk and a speaker for Medtronic, Novo Nordisk, and Sanofi.
Are disparities because of differences in cvd risk factor management?
The question has arisen whether the female/male differences might be because of differences in cardiovascular risk factor management, Simmons noted.
A 2015 American Heart Association statement laid out the evidence for lower prescribing of statins, aspirin, beta-blockers, and ACE inhibitors in women, compared with men, Dr. Simmons said.
And some studies suggest medication adherence is lower in women than men.
In terms of medications, fenofibrate appears to produce better outcomes in women than men, but there is no evidence of gender differences in the effects of statins, ACE inhibitors, or aspirin, Simmons said.
He also outlined the results of a 2008 study of 78,254 patients with acute myocardial infarction from 420 U.S. hospitals in 2001-2006.
Women were older, had more comorbidities, less often presented with ST-elevation myocardial infarction (STEMI), and had a higher rate of unadjusted in-hospital death (8.2% vs. 5.7%; P less than .0001) than men. Of the participants, 33% of women had diabetes, compared with 28% of men.
The in-hospital mortality difference disappeared after multivariable adjustment, but women with STEMI still had higher adjusted mortality rates than men.
“The underuse of evidence-based treatments and delayed reperfusion in women represent potential opportunities for reducing sex disparities in care and outcome after acute myocardial infarction,” the authors concluded.
“It’s very clear amongst our cardiology colleagues that something needs to be done and that we need more aggressive cardiological risk reduction in women,” Dr. Simmons said.
“The AHA has already decided this. It’s already a policy. So why are we having this debate?” he wondered.
He also pointed out that women with prior gestational diabetes are an exceptionally high–risk group, with a twofold excess risk for cardiovascular disease within the first 10 years post partum.
“We need to do something about this particularly high-risk group, independent of debates about gender,” Dr. Simmons emphasized. “Clearly, women with diabetes warrant more aggressive cardiovascular risk reduction than men with diabetes, especially at those younger ages,” he concluded.
No: Confusion about relative risk within each sex and absolute risk
Dr. Davis began his counterargument by stating that estimation of absolute vascular risk is an established part of strategies to prevent cardiovascular disease, including in diabetes.
And that risk, he stressed, is actually higher in men.
“Male sex is a consistent adverse risk factor in cardiovascular disease event prediction equations in type 2 diabetes. Identifying absolute risk is important,” he said, noting risk calculators include male sex, such as the risk engine derived from the United Kingdom Prospective Diabetes Trial.
And in the Australian population-based Fremantle study, of which Dr. Davis is an author, the absolute 5-year incidence rates for all outcomes – including myocardial infarction, stroke, heart failure, lower extremity amputation, cardiovascular mortality, and all-cause mortality – were consistently higher in men versus women in the first phase, which began in the 1990s and included 1,426 individuals with diabetes (91% had type 2 diabetes).
In the ongoing second phase, which began in 2008 with 1,732 participants, overall rates of those outcomes are lower and the discrepancy between men and women has narrowed, Dr. Davis noted.
Overall, the Fremantle study data “suggest that women with type 2 diabetes do not need more aggressive cardiovascular reduction than men with type 2 diabetes because they are not at increased absolute vascular risk,” he stressed.
And in a “sensitivity analysis” of two areas in Finland, the authors concluded that the stronger effect of type 2 diabetes on the risk of congenital heart disease (CHD) in women, compared with men was in part explained by a heavier risk factor burden and a greater effect of blood pressure and atherogenic dyslipidemia in women with diabetes, he explained.
The Finnish authors wrote, “In terms of absolute risk of CHD death or a major CHD event, diabetes almost completely abolished the female protection from CHD.”
But, Dr. Davis emphasized, rates were not higher in females.
So then, “why is there the view that women with type 2 diabetes need more aggressive cardiovascular risk reduction than men with diabetes?
“It probably comes back to confusion based on absolute risk versus a comparison of relative risk within each sex,” he asserted.
ADA Standards of Medical Care 2019 don’t mention gender
Lastly, in a meta-analysis published just in July this year involving more than 5 million participants, compared with men with diabetes, women with diabetes had a 58% and 13% greater risk of CHD and all-cause mortality, respectively.
“This points to an urgent need to develop sex- and gender-specific risk assessment strategies and therapeutic interventions that target diabetes management in the context of CHD prevention,” the authors concluded.
But, Dr. Davis noted, “It is not absolute vascular risk. It’s a relative risk compared across the two genders. In the paper, there is no mention of absolute vascular risk.
“Greater CVD mortality in women with and without diabetes, versus men, doesn’t mean there’s also an absolute vascular increase in women versus men with diabetes,” he said.
Moreover, Dr. Davis pointed out that in an editorial accompanying the 2015 meta-analysis in type 1 diabetes, Simmons had actually stated that absolute mortality rates are highest in men.
“I don’t know what happened to his epidemiology knowledge in the last 4 years but it seems to have gone backwards,” he joked to his debate opponent.
And, Dr. Davis asserted, even if there were a higher risk in women with type 1 diabetes, there is no evidence that cardiovascular risk reduction measures affect endpoints in that patient population. Only about 8% of people with diabetes in statin trials had type 1 diabetes.
Indeed, he noted, in the American Diabetes Association Standards of Medical Care in Diabetes – 2019, the treatment goals for individual cardiovascular risk factors do not mention gender.
What’s more, Dr. David said, there is evidence that women are significantly less likely than men to take prescribed statins and are more likely to have an eating disorder and underdose insulin, “suggesting significant issues with compliance. ... So, trying to get more intensive risk reduction in women may be a challenge.”
“Women with diabetes do not need more aggressive cardiovascular risk reduction than men with diabetes, irrespective of type,” he concluded.
A version of this story originally appeared on medscape.com.
BUSAN, SOUTH KOREA – Whether cardiovascular disease risk reduction efforts should be more aggressive in women than men with diabetes depends on how you interpret the data.
Two experts came to different conclusions on this question during a heated, but jovial, debate last week here at the International Diabetes Federation 2019 Congress.
Endocrinologist David Simmons, MB, BChir, Western Sydney University, Campbelltown, Australia, argued that diabetes erases the well-described life expectancy advantage of 4-7 years that women experience over men in the general population.
He also highlighted the fact that the heightened risk is of particular concern in both younger women and those with prior gestational diabetes.
But Timothy Davis, BMedSc, MB, BS, DPhil, an endocrinologist and general physician at Fremantle (Australia) Hospital, countered that the data only show the diabetes-attributable excess cardiovascular risk is higher in women than men, but that the absolute risk is actually greater in men.
Moreover, he argued, at least in type 1 diabetes, there is no evidence that more aggressive cardiovascular risk factor management improves outcomes.
Yes: Diabetes eliminates female CVD protection
Dr. Simmons began by pointing out that, although on average women die at an older age than men, it has been known for over 40 years that this “female protection” is lost in insulin-treated women, particularly as a result of their increased risk for cardiovascular disease.
In a 2015 meta-analysis of 26 studies, women with type 1 diabetes were found to have about a 37% greater risk of all-cause mortality, compared with men with the condition when mortality is contrasted with that of the general population, and twice the risk of both fatal and nonfatal vascular events.
The risk appeared to be greater in women who were younger at the time of diabetes diagnosis. “This is a really important point – the time we would want to intervene,” Dr. Simmons said.
In another meta-analysis of 30 studies including 2,307,694 individuals with type 2 diabetes and 252,491 deaths, the pooled women-to-men ratio of the standardized mortality ratio for all-cause mortality was 1.14.
In those with versus without type 2 diabetes, the pooled standardized mortality ratio in women was 2.30 and in men was 1.94, both significant, compared with those without diabetes.
And in a 2006 meta-analysis of 22 studies involving individuals with type 2 diabetes, the pooled data showed a 46% excess relative risk using standardized mortality ratios in women versus men for fatal coronary artery disease.
Meanwhile, in a 2018 meta-analysis of 68 studies involving nearly 1 million adults examining differences in occlusive vascular disease, after controlling for major vascular risk factors, diabetes roughly doubled the risk for occlusive vascular mortality in men (relative risk, 2.10), but tripled it in women (3.00).
Women with diabetes aged 35-59 years had the highest relative risk for death over follow-up across all age and sex groups: They had 5.5 times the excess risk, compared with those without diabetes, while the excess risk for men of that age was 2.3-fold.
“So very clearly, it’s these young women who are most at risk, “emphasized Dr. Simmons, who is an investigator for Novo Nordisk and a speaker for Medtronic, Novo Nordisk, and Sanofi.
Are disparities because of differences in cvd risk factor management?
The question has arisen whether the female/male differences might be because of differences in cardiovascular risk factor management, Simmons noted.
A 2015 American Heart Association statement laid out the evidence for lower prescribing of statins, aspirin, beta-blockers, and ACE inhibitors in women, compared with men, Dr. Simmons said.
And some studies suggest medication adherence is lower in women than men.
In terms of medications, fenofibrate appears to produce better outcomes in women than men, but there is no evidence of gender differences in the effects of statins, ACE inhibitors, or aspirin, Simmons said.
He also outlined the results of a 2008 study of 78,254 patients with acute myocardial infarction from 420 U.S. hospitals in 2001-2006.
Women were older, had more comorbidities, less often presented with ST-elevation myocardial infarction (STEMI), and had a higher rate of unadjusted in-hospital death (8.2% vs. 5.7%; P less than .0001) than men. Of the participants, 33% of women had diabetes, compared with 28% of men.
The in-hospital mortality difference disappeared after multivariable adjustment, but women with STEMI still had higher adjusted mortality rates than men.
“The underuse of evidence-based treatments and delayed reperfusion in women represent potential opportunities for reducing sex disparities in care and outcome after acute myocardial infarction,” the authors concluded.
“It’s very clear amongst our cardiology colleagues that something needs to be done and that we need more aggressive cardiological risk reduction in women,” Dr. Simmons said.
“The AHA has already decided this. It’s already a policy. So why are we having this debate?” he wondered.
He also pointed out that women with prior gestational diabetes are an exceptionally high–risk group, with a twofold excess risk for cardiovascular disease within the first 10 years post partum.
“We need to do something about this particularly high-risk group, independent of debates about gender,” Dr. Simmons emphasized. “Clearly, women with diabetes warrant more aggressive cardiovascular risk reduction than men with diabetes, especially at those younger ages,” he concluded.
No: Confusion about relative risk within each sex and absolute risk
Dr. Davis began his counterargument by stating that estimation of absolute vascular risk is an established part of strategies to prevent cardiovascular disease, including in diabetes.
And that risk, he stressed, is actually higher in men.
“Male sex is a consistent adverse risk factor in cardiovascular disease event prediction equations in type 2 diabetes. Identifying absolute risk is important,” he said, noting risk calculators include male sex, such as the risk engine derived from the United Kingdom Prospective Diabetes Trial.
And in the Australian population-based Fremantle study, of which Dr. Davis is an author, the absolute 5-year incidence rates for all outcomes – including myocardial infarction, stroke, heart failure, lower extremity amputation, cardiovascular mortality, and all-cause mortality – were consistently higher in men versus women in the first phase, which began in the 1990s and included 1,426 individuals with diabetes (91% had type 2 diabetes).
In the ongoing second phase, which began in 2008 with 1,732 participants, overall rates of those outcomes are lower and the discrepancy between men and women has narrowed, Dr. Davis noted.
Overall, the Fremantle study data “suggest that women with type 2 diabetes do not need more aggressive cardiovascular reduction than men with type 2 diabetes because they are not at increased absolute vascular risk,” he stressed.
And in a “sensitivity analysis” of two areas in Finland, the authors concluded that the stronger effect of type 2 diabetes on the risk of congenital heart disease (CHD) in women, compared with men was in part explained by a heavier risk factor burden and a greater effect of blood pressure and atherogenic dyslipidemia in women with diabetes, he explained.
The Finnish authors wrote, “In terms of absolute risk of CHD death or a major CHD event, diabetes almost completely abolished the female protection from CHD.”
But, Dr. Davis emphasized, rates were not higher in females.
So then, “why is there the view that women with type 2 diabetes need more aggressive cardiovascular risk reduction than men with diabetes?
“It probably comes back to confusion based on absolute risk versus a comparison of relative risk within each sex,” he asserted.
ADA Standards of Medical Care 2019 don’t mention gender
Lastly, in a meta-analysis published just in July this year involving more than 5 million participants, compared with men with diabetes, women with diabetes had a 58% and 13% greater risk of CHD and all-cause mortality, respectively.
“This points to an urgent need to develop sex- and gender-specific risk assessment strategies and therapeutic interventions that target diabetes management in the context of CHD prevention,” the authors concluded.
But, Dr. Davis noted, “It is not absolute vascular risk. It’s a relative risk compared across the two genders. In the paper, there is no mention of absolute vascular risk.
“Greater CVD mortality in women with and without diabetes, versus men, doesn’t mean there’s also an absolute vascular increase in women versus men with diabetes,” he said.
Moreover, Dr. Davis pointed out that in an editorial accompanying the 2015 meta-analysis in type 1 diabetes, Simmons had actually stated that absolute mortality rates are highest in men.
“I don’t know what happened to his epidemiology knowledge in the last 4 years but it seems to have gone backwards,” he joked to his debate opponent.
And, Dr. Davis asserted, even if there were a higher risk in women with type 1 diabetes, there is no evidence that cardiovascular risk reduction measures affect endpoints in that patient population. Only about 8% of people with diabetes in statin trials had type 1 diabetes.
Indeed, he noted, in the American Diabetes Association Standards of Medical Care in Diabetes – 2019, the treatment goals for individual cardiovascular risk factors do not mention gender.
What’s more, Dr. David said, there is evidence that women are significantly less likely than men to take prescribed statins and are more likely to have an eating disorder and underdose insulin, “suggesting significant issues with compliance. ... So, trying to get more intensive risk reduction in women may be a challenge.”
“Women with diabetes do not need more aggressive cardiovascular risk reduction than men with diabetes, irrespective of type,” he concluded.
A version of this story originally appeared on medscape.com.
Ten-year results support partial breast irradiation
SAN ANTONIO – For patients with early, low-risk breast cancer, accelerated partial breast irradiation (APBI) may be considered a standard alternative to whole breast irradiation, according to investigators.
This conclusion was based on 10-year follow-up results from the APBI IMRT Florence phase III trial, which showed that APBI was associated with significantly fewer adverse events and better cosmetic results than whole breast irradiation without increasing risks of tumor recurrence or mortality, reported lead author Irco Meattini, MD, of the University of Florence, Italy, and colleagues.
“As we well know, recent developments in radiation oncology ... show a move toward a deescalation strategy for early breast cancer, including accelerated and nonaccelerated partial breast irradiation,” Dr. Meattini said during a presentation at the San Antonio Breast Cancer Symposium. “What we have learned from [previous] phase 3 trials [is that with adequate patient selection for] partial breast irradiation, safety profile and cosmetic outcome are strongly associated with technique – the approach, the dose, the number of fractions per day, and the total dose.”
The current phase 3 trial, which enrolled 520 patients with early breast cancer, aimed to determine long-term efficacy, safety, and cosmetic outcomes for partial versus whole breast irradiation. All patients enrolled were at least 40 years of age and had a maximum pathological tumor size of 25 mm. Patients were randomized in a 1:1 ratio to receive either whole breast irradiation (WBI) at a dose of 50 Gy in 25 fractions, followed by 10 Gy in five fractions delivered to the tumor bed; or APBI, which was delivered to the tumor bed at a dose of 30 Gy in five daily fractions.
The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were overall survival, breast cancer–specific survival, distant metastasis-free survival, locoregional recurrences, and contralateral breast cancer. Adverse events and cosmesis also were evaluated.
Five-year results, previously reported, revealed no significant difference in survival rates or IBTR between treatment techniques, and results of the present 10-year analysis maintained these findings. Between groups, no significant differences were observed in any of the primary or secondary endpoints, suggesting that major efficacy outcomes were unaffected by type of irradiation delivered.
While major efficacy endpoints were comparable between groups, safety profiles and cosmetic results differed significantly.
Adverse events of all levels of severity were significantly more common with WBI than APBI. Grade 2 or higher acute adverse events occurred in 37.7% of patients treated with WBI, compared with just 2.0% of patients treated with APBI (P = .0001). The rate of grade 2 or higher adverse events was also significantly higher in the WBI group than in the APBI group in the late setting, albeit with a narrower margin than in the acute setting (2.7% vs 0%; P = .015). Skin toxicity rates followed a similar pattern, favoring APBI both in the acute phase (66.5% vs. 21.1%; P = .0001) and the late phase (30.0% vs. 4.5%; P = .0001).
In further support of APBI, cosmetic results, as measured by the Harvard Breast Cosmesis Scale, were significantly better in the APBI group than in the WBI group. Both physicians and patients were significantly more likely to report good or excellent cosmetic results with APBI than WBI.
“APBI might be considered a standard alternative to WBI in low risk and very low risk early breast cancer patients,” Dr. Meattini concluded.
The investigators reported no disclosures.
SOURCE: Meattini et al. SABCS. 2019 Dec 12. Abstract GS4-06.
SAN ANTONIO – For patients with early, low-risk breast cancer, accelerated partial breast irradiation (APBI) may be considered a standard alternative to whole breast irradiation, according to investigators.
This conclusion was based on 10-year follow-up results from the APBI IMRT Florence phase III trial, which showed that APBI was associated with significantly fewer adverse events and better cosmetic results than whole breast irradiation without increasing risks of tumor recurrence or mortality, reported lead author Irco Meattini, MD, of the University of Florence, Italy, and colleagues.
“As we well know, recent developments in radiation oncology ... show a move toward a deescalation strategy for early breast cancer, including accelerated and nonaccelerated partial breast irradiation,” Dr. Meattini said during a presentation at the San Antonio Breast Cancer Symposium. “What we have learned from [previous] phase 3 trials [is that with adequate patient selection for] partial breast irradiation, safety profile and cosmetic outcome are strongly associated with technique – the approach, the dose, the number of fractions per day, and the total dose.”
The current phase 3 trial, which enrolled 520 patients with early breast cancer, aimed to determine long-term efficacy, safety, and cosmetic outcomes for partial versus whole breast irradiation. All patients enrolled were at least 40 years of age and had a maximum pathological tumor size of 25 mm. Patients were randomized in a 1:1 ratio to receive either whole breast irradiation (WBI) at a dose of 50 Gy in 25 fractions, followed by 10 Gy in five fractions delivered to the tumor bed; or APBI, which was delivered to the tumor bed at a dose of 30 Gy in five daily fractions.
The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were overall survival, breast cancer–specific survival, distant metastasis-free survival, locoregional recurrences, and contralateral breast cancer. Adverse events and cosmesis also were evaluated.
Five-year results, previously reported, revealed no significant difference in survival rates or IBTR between treatment techniques, and results of the present 10-year analysis maintained these findings. Between groups, no significant differences were observed in any of the primary or secondary endpoints, suggesting that major efficacy outcomes were unaffected by type of irradiation delivered.
While major efficacy endpoints were comparable between groups, safety profiles and cosmetic results differed significantly.
Adverse events of all levels of severity were significantly more common with WBI than APBI. Grade 2 or higher acute adverse events occurred in 37.7% of patients treated with WBI, compared with just 2.0% of patients treated with APBI (P = .0001). The rate of grade 2 or higher adverse events was also significantly higher in the WBI group than in the APBI group in the late setting, albeit with a narrower margin than in the acute setting (2.7% vs 0%; P = .015). Skin toxicity rates followed a similar pattern, favoring APBI both in the acute phase (66.5% vs. 21.1%; P = .0001) and the late phase (30.0% vs. 4.5%; P = .0001).
In further support of APBI, cosmetic results, as measured by the Harvard Breast Cosmesis Scale, were significantly better in the APBI group than in the WBI group. Both physicians and patients were significantly more likely to report good or excellent cosmetic results with APBI than WBI.
“APBI might be considered a standard alternative to WBI in low risk and very low risk early breast cancer patients,” Dr. Meattini concluded.
The investigators reported no disclosures.
SOURCE: Meattini et al. SABCS. 2019 Dec 12. Abstract GS4-06.
SAN ANTONIO – For patients with early, low-risk breast cancer, accelerated partial breast irradiation (APBI) may be considered a standard alternative to whole breast irradiation, according to investigators.
This conclusion was based on 10-year follow-up results from the APBI IMRT Florence phase III trial, which showed that APBI was associated with significantly fewer adverse events and better cosmetic results than whole breast irradiation without increasing risks of tumor recurrence or mortality, reported lead author Irco Meattini, MD, of the University of Florence, Italy, and colleagues.
“As we well know, recent developments in radiation oncology ... show a move toward a deescalation strategy for early breast cancer, including accelerated and nonaccelerated partial breast irradiation,” Dr. Meattini said during a presentation at the San Antonio Breast Cancer Symposium. “What we have learned from [previous] phase 3 trials [is that with adequate patient selection for] partial breast irradiation, safety profile and cosmetic outcome are strongly associated with technique – the approach, the dose, the number of fractions per day, and the total dose.”
The current phase 3 trial, which enrolled 520 patients with early breast cancer, aimed to determine long-term efficacy, safety, and cosmetic outcomes for partial versus whole breast irradiation. All patients enrolled were at least 40 years of age and had a maximum pathological tumor size of 25 mm. Patients were randomized in a 1:1 ratio to receive either whole breast irradiation (WBI) at a dose of 50 Gy in 25 fractions, followed by 10 Gy in five fractions delivered to the tumor bed; or APBI, which was delivered to the tumor bed at a dose of 30 Gy in five daily fractions.
The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were overall survival, breast cancer–specific survival, distant metastasis-free survival, locoregional recurrences, and contralateral breast cancer. Adverse events and cosmesis also were evaluated.
Five-year results, previously reported, revealed no significant difference in survival rates or IBTR between treatment techniques, and results of the present 10-year analysis maintained these findings. Between groups, no significant differences were observed in any of the primary or secondary endpoints, suggesting that major efficacy outcomes were unaffected by type of irradiation delivered.
While major efficacy endpoints were comparable between groups, safety profiles and cosmetic results differed significantly.
Adverse events of all levels of severity were significantly more common with WBI than APBI. Grade 2 or higher acute adverse events occurred in 37.7% of patients treated with WBI, compared with just 2.0% of patients treated with APBI (P = .0001). The rate of grade 2 or higher adverse events was also significantly higher in the WBI group than in the APBI group in the late setting, albeit with a narrower margin than in the acute setting (2.7% vs 0%; P = .015). Skin toxicity rates followed a similar pattern, favoring APBI both in the acute phase (66.5% vs. 21.1%; P = .0001) and the late phase (30.0% vs. 4.5%; P = .0001).
In further support of APBI, cosmetic results, as measured by the Harvard Breast Cosmesis Scale, were significantly better in the APBI group than in the WBI group. Both physicians and patients were significantly more likely to report good or excellent cosmetic results with APBI than WBI.
“APBI might be considered a standard alternative to WBI in low risk and very low risk early breast cancer patients,” Dr. Meattini concluded.
The investigators reported no disclosures.
SOURCE: Meattini et al. SABCS. 2019 Dec 12. Abstract GS4-06.
REPORTING FROM SABCS 2019
Improving sepsis-related outcomes
Early diagnosis a key goal
Sepsis is a leading cause of death and disease among patients in hospitals, and it’s the subject of a recent quality improvement study in the Journal for Healthcare Quality.
“The number of cases per year has been increasing in the U.S., and it is the most expensive condition treated in U.S. hospitals,” said lead author M. Courtney Hughes, PhD, of Northern Illinois University in DeKalb.
But early identification of symptoms can be complex and difficult for clinicians, meaning there’s a continuing need for research studies examining sepsis identification and prevention. “The purpose of this study was to examine a quality improvement project that consisted of clinical alerts, audit and feedback, and staff education at an integrated health care system in the Midwest,” she said.
In a retrospective analysis, the researchers examined data from three health systems to determine the impact of a 10-month sepsis quality improvement program that consisted of clinical alerts, audit and feedback, and staff education. The results showed that, compared with the control group, the intervention group significantly decreased length of stay and costs per stay.
“One way to improve sepsis health outcomes and decrease costs may be for hospitals to implement a sepsis quality improvement program,” Dr. Hughes said. “Also, providing sepsis performance data and education to hospital providers and administrators can arm staff with the knowledge and tools necessary for improving processes and performance related to sepsis.”
Dr. Hughes said that she hopes this work will encourage hospitalists to seek sepsis-related performance data and training. “By doing so, they may help achieve earlier diagnosis of sepsis cases and initiation of the Surviving Sepsis Campaign bundle.”
Reference
Hughes MC et al. A quality improvement project to improve sepsis-related outcomes at an integrated healthcare system. J Healthc Qual. Published online 2019 Mar 14. doi: 10.1097/JHQ.0000000000000193.
Early diagnosis a key goal
Early diagnosis a key goal
Sepsis is a leading cause of death and disease among patients in hospitals, and it’s the subject of a recent quality improvement study in the Journal for Healthcare Quality.
“The number of cases per year has been increasing in the U.S., and it is the most expensive condition treated in U.S. hospitals,” said lead author M. Courtney Hughes, PhD, of Northern Illinois University in DeKalb.
But early identification of symptoms can be complex and difficult for clinicians, meaning there’s a continuing need for research studies examining sepsis identification and prevention. “The purpose of this study was to examine a quality improvement project that consisted of clinical alerts, audit and feedback, and staff education at an integrated health care system in the Midwest,” she said.
In a retrospective analysis, the researchers examined data from three health systems to determine the impact of a 10-month sepsis quality improvement program that consisted of clinical alerts, audit and feedback, and staff education. The results showed that, compared with the control group, the intervention group significantly decreased length of stay and costs per stay.
“One way to improve sepsis health outcomes and decrease costs may be for hospitals to implement a sepsis quality improvement program,” Dr. Hughes said. “Also, providing sepsis performance data and education to hospital providers and administrators can arm staff with the knowledge and tools necessary for improving processes and performance related to sepsis.”
Dr. Hughes said that she hopes this work will encourage hospitalists to seek sepsis-related performance data and training. “By doing so, they may help achieve earlier diagnosis of sepsis cases and initiation of the Surviving Sepsis Campaign bundle.”
Reference
Hughes MC et al. A quality improvement project to improve sepsis-related outcomes at an integrated healthcare system. J Healthc Qual. Published online 2019 Mar 14. doi: 10.1097/JHQ.0000000000000193.
Sepsis is a leading cause of death and disease among patients in hospitals, and it’s the subject of a recent quality improvement study in the Journal for Healthcare Quality.
“The number of cases per year has been increasing in the U.S., and it is the most expensive condition treated in U.S. hospitals,” said lead author M. Courtney Hughes, PhD, of Northern Illinois University in DeKalb.
But early identification of symptoms can be complex and difficult for clinicians, meaning there’s a continuing need for research studies examining sepsis identification and prevention. “The purpose of this study was to examine a quality improvement project that consisted of clinical alerts, audit and feedback, and staff education at an integrated health care system in the Midwest,” she said.
In a retrospective analysis, the researchers examined data from three health systems to determine the impact of a 10-month sepsis quality improvement program that consisted of clinical alerts, audit and feedback, and staff education. The results showed that, compared with the control group, the intervention group significantly decreased length of stay and costs per stay.
“One way to improve sepsis health outcomes and decrease costs may be for hospitals to implement a sepsis quality improvement program,” Dr. Hughes said. “Also, providing sepsis performance data and education to hospital providers and administrators can arm staff with the knowledge and tools necessary for improving processes and performance related to sepsis.”
Dr. Hughes said that she hopes this work will encourage hospitalists to seek sepsis-related performance data and training. “By doing so, they may help achieve earlier diagnosis of sepsis cases and initiation of the Surviving Sepsis Campaign bundle.”
Reference
Hughes MC et al. A quality improvement project to improve sepsis-related outcomes at an integrated healthcare system. J Healthc Qual. Published online 2019 Mar 14. doi: 10.1097/JHQ.0000000000000193.
The Great Pretender
Susannah Cahalan’s new book challenges an experiment that changed psychiatry
As an undergraduate psychology major, I was taught about the Rosenhan study in several of my courses. My professors lectured about the shocking findings psychologist David Rosenhan, PhD, documented in a 1973 Science article, “On Being Sane in Insane Places” and these findings lent themselves to lecture hall drama. Eight people presented to hospitals and said they heard voices saying: “empty, hollow, thud.” These “pseudopatients” exhibited no other psychiatric symptoms but were admitted, diagnosed with schizophrenia, and observations of their behavior were made. The charts included notes such as, “Patient exhibits writing behavior,” my professors said. The pseudopatients were kept for an average of 19 days, and one for as long as 51 days. The decades have passed, and there are many things I learned in college that I have since forgotten, but I remember “empty, hollow, thud,” and the famous Rosenhan experiment.
I was eager to read Susannah Cahalan’s book, “The Great Pretender” (Grand Central Publishing, 2019), which puts both Dr. Rosenhan and his pseudopatient study under a microscope. Ms. Cahalan is the author of the page-turner, Brain on Fire: My Month of Madness (Free Press, 2012), where she recounted her own struggle with a psychotic episode. Ms. Cahalan, a young reporter in New York City, became psychotic and then catatonic; her condition perplexed the neurologists who were treating her on an inpatient unit, and they were on the verge of transferring her to psychiatry when a diagnosis of anti-NMDA receptor encephalitis was suspected and then confirmed with a brain biopsy. Ms. Cahalan made a full recovery after treatment with steroids, intravenous immunoglobulin, and plasmapheresis. While Ms. Cahalan’s symptoms were classic for a severe psychotic disorder, there was reason to believe that this was not a primary psychiatric disorder: She was having grand mal seizures. Her book was a bestseller, and she has spoken widely to make others aware of this rare illness that masquerades as psychosis. I heard her speak at the opening session of the American Psychiatric Association’s annual meeting in May of 2017.“My family, like many families before them, fought against the tyranny of the mental illness label,” Ms. Cahalan writes at the very beginning of “The Great Pretender.” She goes on to talk about how psychiatry differs from other medical fields: It’s the only specialty where people can be treated against their will; psychiatry casts judgments on the person; mental illness is poorly defined – perhaps there is no clear divide between normal and mad; and psychiatric disorders are less “real” than other illnesses. Throughout the book she refers to psychiatrists as smug and arrogant.
Ms. Cahalan takes on the task of documenting the horrors of psychiatry’s often sordid history, starting with journalist Nellie Bly’s 1887 journey into to a psychiatric facility to expose the abuses there. Certainly, psychiatry’s history is sordid. Ms. Cahalan talks about inhumane conditions in overcrowded psychiatric hospitals, about our sad chapter of lobotomies, about the influence of psychoanalysis on diagnosis and treatment, and about how homosexuality was once an illness and now is not. She includes “One Flew Over the Cuckoo’s Nest,” “The Myth of Mental Illness,” big pharma, and the Goldwater fiasco. In her recounting of the history, it’s all bad. She mentions Benjamin Rush, MD, only once, as the creator of “ ‘... the tranquilizing chair’ (a case of the worst false advertising ever), a terrifying sensory-deprivation apparatus in which patients were strapped down to a chair with a wooden box placed over their heads to block stimulation, restrict movement, and reduce blood to the brain.” Dr. Rush’s role as the father of American psychiatry who challenged the belief that mental illness was the result of demonic possession, gets no mention. Nor does Ms. Cahalan note that he founded Pennsylvania Hospital, where moral and occupational therapy revolutionized the treatment of those with mental illness.
So there’s her story, her rendition of the history of American psychiatry, and through this she weaves in the story of the Rosenhan experiment.
“ ‘It all started out as a dare,’ Dr. Rosenhan told a local newspaper, ‘I was teaching psychology at Swarthmore, and my students were saying that the course was too conceptual and abstract. So I said, ‘Okay, if you really want to know what mental patients are like, become mental patients.’ ”
Really? I read this and wondered how a psychologist could talk about people who had been hospitalized with psychiatric disorders as though they were aliens. Certainly, some of these students, their family members, or their friends must have been hospitalized at some point. Yet all through, there is this sense that the patients are other, and the discovery of the undercover operation is that the patients are actually human beings! Dr. Rosenhan, who was one of the pseudopatients, goes on to conclude that the label is everything, that once labeled they are treated differently by the nurses in “cages” and the doctors who walk by and avert their gaze. A second man Ms. Cahalan named, also one of the pseudopatients, had a similar experience. A third subject she located was not included in the study: His experience was counter to the findings of the study, his time in the hospital was a positive, he found it comforting, and the experiences he had there had a lasting positive influence on his life.
Ms. Cahalan talks about the publication of “On Being Sane in Insane Places” as a study that was finally scientific, one that changed all of psychiatry, and was the driving force for the creation of the DSM-III and the closure of state hospitals. I wondered if it was as influential as Ms. Cahalan claims, and I asked some psychiatrists who were practicing in 1973 when the article was published. I wanted to know if this study rocked their world.
“At first, with the great amount of publicity the study generated, it was added fodder for the antipsychiatrists, including the Scientologists and Szaszians,” Steven Sharfstein, MD, a former president of the American Psychiatric Association, told me. “But as young psychiatrists in the trenches, business continued to boom, and we continued to do the best job we could with diagnosis, assessment of risk, involuntary commitment, and treatment. And from what I recall, morale was high in the 1970s. We had some new medications and psychotherapies, and there was community activism. Faking symptoms to gain admission seemed to be a no-brainer, but keeping people for long stays was more problematic.”
E. Fuller Torrey, MD, the founder of the Treatment Advocacy Center who worked for many years treating patients at St. Elizabeth’s Hospital, replied: “It is important to remember that this study was published at the height of the deinstitutionalization movement and quite likely accelerated it. As I recall, at the time it seemed odd that all eight patients claimed to have had similar experiences while hospitalized. I think the main effect of the study was to provide ammunition for the antipsychiatrists.”
Ms. Cahalan has bought into the antipsychiatry movement full force. It’s not until the very end that there is any acknowledgment that psychiatry ever helped anyone, and even then, it’s a bit begrudging. Worse, she neglects to mention that people with psychiatric disorders suffer because of their psychic pain; one could get through this book and believe that people with mental illness struggle only because they are labeled and then mistreated, and for someone who has suffered herself, she misses the essence of how awful it is to be ill, and that people are often helped by psychiatric treatments. When she finally adds a paragraph talking about the usefulness of psychotropics, it’s with a caveat. “But I’m not here to rail against the drugs. There are plenty of places you can get that perspective. I see that these drugs help many people lead full and meaningful lives. It would be folly to discount their worth. We also can’t deny that the situation is complicated.”
There are moments in the manuscript where I found it difficult to know what were Dr. Rosenhan’s interpretations and what were Ms. Callahan’s interpretations of Dr. Rosenhan’s experiences. A lot of assumptions are made – particularly about the motivations of the hospital staff – and I wasn’t always sure they were correct. For example, on his second day in the hospital, Dr. Rosenhan asked a nurse for the newspaper. When she tells him it hasn’t come yet, he concludes that the staff is keeping the newspapers from the patients. And when a staff member is initially chatty then later shuns Dr. Rosenhan, he concludes that the man initially mistook him for a psychiatrist because he looks professorial. Both Ms. Cahalan and Dr. Rosenhan approach psychiatry with biases, and they don’t always question their assumptions.
, a professor who didn’t treat patients. This intermixing of the two fields felt contrived to me, and gave too much credence to the idea that no one really knows sane from disordered, and everyone was embracing the antipsychiatry dogma. Surely, someone during the those years must have liked their psychiatrist.
That said, Ms. Cahalan does a phenomenal job of infiltrating the world of the late Dr. Rosenhan. She starts out enamored by him and by his finding that psychiatrists can’t tell real illness from faked disorder. She meets with his friends, his son, his colleagues, his students, and she flies all over the country to meet with those who can help her understand him. She gains access to his personal files and to the book he started to write about the experiment, then abandoned, which eventually resulted in a lawsuit by Doubleday to have the book’s advance returned. At one point, she even hires a private detective.
What is Ms. Cahalan looking for so desperately? She’s looking for these anonymous pseudopatients, the people who were admitted to these unnamed state hospitals, who made observations and took notes, who were diagnosed with schizophrenia and then finally released. She’s looking for the truth, and while she identifies Dr. Rosenhan and two other pseudopatients as people who faked their way into the hospital, she finds a mass of contradictions. The one pseudopatient was excluded from the study – he is the one who felt comforted by his time in the hospital. The other six pseudopatients could not be found, despite Ms. Cahalan’s heroic attempts. Furthermore, she found many inconsistencies in what Dr. Rosenhan reported, and his hospital notes revealed more than a presentation for voices saying “empty, hollow, thud.” He reported it had been going on for months, that he had put copper over his ears to block the sound, and that he felt suicidal.
Ultimately, Ms. Cahalan was left to conclude that the Rosenhan experiment was a lie, that the pseudopatients likely never existed and the article was a fabrication. She brings up other studies that have been proven to be fraudulent, and by this point, our faith in all of science is pretty shaken.
Ms. Cahalan took a long journey to get us to this place, one that spent a lot of effort in bashing psychiatry, finally concluding that, as a result of this fraudulent experiment, too many hospitals have been shuttered – leaving our sickest patients to the streets and to the jails – and that there are not enough mental health professionals. As a psychiatrist – one who is often willing to question our practices – I was distracted by the flagrant antipsychiatry sentiments. Reading past that, Ms. Cahalan’s remarkable detective work and creative intermingling of the Rosenhan experiment layered on the history of psychiatry, further layered on her own experience with psychosis, makes for an amazing story. The Rosenhan study may have rocked the world of psychiatry; the fact that it was fabricated should rock us even more.
Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.
Susannah Cahalan’s new book challenges an experiment that changed psychiatry
Susannah Cahalan’s new book challenges an experiment that changed psychiatry
As an undergraduate psychology major, I was taught about the Rosenhan study in several of my courses. My professors lectured about the shocking findings psychologist David Rosenhan, PhD, documented in a 1973 Science article, “On Being Sane in Insane Places” and these findings lent themselves to lecture hall drama. Eight people presented to hospitals and said they heard voices saying: “empty, hollow, thud.” These “pseudopatients” exhibited no other psychiatric symptoms but were admitted, diagnosed with schizophrenia, and observations of their behavior were made. The charts included notes such as, “Patient exhibits writing behavior,” my professors said. The pseudopatients were kept for an average of 19 days, and one for as long as 51 days. The decades have passed, and there are many things I learned in college that I have since forgotten, but I remember “empty, hollow, thud,” and the famous Rosenhan experiment.
I was eager to read Susannah Cahalan’s book, “The Great Pretender” (Grand Central Publishing, 2019), which puts both Dr. Rosenhan and his pseudopatient study under a microscope. Ms. Cahalan is the author of the page-turner, Brain on Fire: My Month of Madness (Free Press, 2012), where she recounted her own struggle with a psychotic episode. Ms. Cahalan, a young reporter in New York City, became psychotic and then catatonic; her condition perplexed the neurologists who were treating her on an inpatient unit, and they were on the verge of transferring her to psychiatry when a diagnosis of anti-NMDA receptor encephalitis was suspected and then confirmed with a brain biopsy. Ms. Cahalan made a full recovery after treatment with steroids, intravenous immunoglobulin, and plasmapheresis. While Ms. Cahalan’s symptoms were classic for a severe psychotic disorder, there was reason to believe that this was not a primary psychiatric disorder: She was having grand mal seizures. Her book was a bestseller, and she has spoken widely to make others aware of this rare illness that masquerades as psychosis. I heard her speak at the opening session of the American Psychiatric Association’s annual meeting in May of 2017.“My family, like many families before them, fought against the tyranny of the mental illness label,” Ms. Cahalan writes at the very beginning of “The Great Pretender.” She goes on to talk about how psychiatry differs from other medical fields: It’s the only specialty where people can be treated against their will; psychiatry casts judgments on the person; mental illness is poorly defined – perhaps there is no clear divide between normal and mad; and psychiatric disorders are less “real” than other illnesses. Throughout the book she refers to psychiatrists as smug and arrogant.
Ms. Cahalan takes on the task of documenting the horrors of psychiatry’s often sordid history, starting with journalist Nellie Bly’s 1887 journey into to a psychiatric facility to expose the abuses there. Certainly, psychiatry’s history is sordid. Ms. Cahalan talks about inhumane conditions in overcrowded psychiatric hospitals, about our sad chapter of lobotomies, about the influence of psychoanalysis on diagnosis and treatment, and about how homosexuality was once an illness and now is not. She includes “One Flew Over the Cuckoo’s Nest,” “The Myth of Mental Illness,” big pharma, and the Goldwater fiasco. In her recounting of the history, it’s all bad. She mentions Benjamin Rush, MD, only once, as the creator of “ ‘... the tranquilizing chair’ (a case of the worst false advertising ever), a terrifying sensory-deprivation apparatus in which patients were strapped down to a chair with a wooden box placed over their heads to block stimulation, restrict movement, and reduce blood to the brain.” Dr. Rush’s role as the father of American psychiatry who challenged the belief that mental illness was the result of demonic possession, gets no mention. Nor does Ms. Cahalan note that he founded Pennsylvania Hospital, where moral and occupational therapy revolutionized the treatment of those with mental illness.
So there’s her story, her rendition of the history of American psychiatry, and through this she weaves in the story of the Rosenhan experiment.
“ ‘It all started out as a dare,’ Dr. Rosenhan told a local newspaper, ‘I was teaching psychology at Swarthmore, and my students were saying that the course was too conceptual and abstract. So I said, ‘Okay, if you really want to know what mental patients are like, become mental patients.’ ”
Really? I read this and wondered how a psychologist could talk about people who had been hospitalized with psychiatric disorders as though they were aliens. Certainly, some of these students, their family members, or their friends must have been hospitalized at some point. Yet all through, there is this sense that the patients are other, and the discovery of the undercover operation is that the patients are actually human beings! Dr. Rosenhan, who was one of the pseudopatients, goes on to conclude that the label is everything, that once labeled they are treated differently by the nurses in “cages” and the doctors who walk by and avert their gaze. A second man Ms. Cahalan named, also one of the pseudopatients, had a similar experience. A third subject she located was not included in the study: His experience was counter to the findings of the study, his time in the hospital was a positive, he found it comforting, and the experiences he had there had a lasting positive influence on his life.
Ms. Cahalan talks about the publication of “On Being Sane in Insane Places” as a study that was finally scientific, one that changed all of psychiatry, and was the driving force for the creation of the DSM-III and the closure of state hospitals. I wondered if it was as influential as Ms. Cahalan claims, and I asked some psychiatrists who were practicing in 1973 when the article was published. I wanted to know if this study rocked their world.
“At first, with the great amount of publicity the study generated, it was added fodder for the antipsychiatrists, including the Scientologists and Szaszians,” Steven Sharfstein, MD, a former president of the American Psychiatric Association, told me. “But as young psychiatrists in the trenches, business continued to boom, and we continued to do the best job we could with diagnosis, assessment of risk, involuntary commitment, and treatment. And from what I recall, morale was high in the 1970s. We had some new medications and psychotherapies, and there was community activism. Faking symptoms to gain admission seemed to be a no-brainer, but keeping people for long stays was more problematic.”
E. Fuller Torrey, MD, the founder of the Treatment Advocacy Center who worked for many years treating patients at St. Elizabeth’s Hospital, replied: “It is important to remember that this study was published at the height of the deinstitutionalization movement and quite likely accelerated it. As I recall, at the time it seemed odd that all eight patients claimed to have had similar experiences while hospitalized. I think the main effect of the study was to provide ammunition for the antipsychiatrists.”
Ms. Cahalan has bought into the antipsychiatry movement full force. It’s not until the very end that there is any acknowledgment that psychiatry ever helped anyone, and even then, it’s a bit begrudging. Worse, she neglects to mention that people with psychiatric disorders suffer because of their psychic pain; one could get through this book and believe that people with mental illness struggle only because they are labeled and then mistreated, and for someone who has suffered herself, she misses the essence of how awful it is to be ill, and that people are often helped by psychiatric treatments. When she finally adds a paragraph talking about the usefulness of psychotropics, it’s with a caveat. “But I’m not here to rail against the drugs. There are plenty of places you can get that perspective. I see that these drugs help many people lead full and meaningful lives. It would be folly to discount their worth. We also can’t deny that the situation is complicated.”
There are moments in the manuscript where I found it difficult to know what were Dr. Rosenhan’s interpretations and what were Ms. Callahan’s interpretations of Dr. Rosenhan’s experiences. A lot of assumptions are made – particularly about the motivations of the hospital staff – and I wasn’t always sure they were correct. For example, on his second day in the hospital, Dr. Rosenhan asked a nurse for the newspaper. When she tells him it hasn’t come yet, he concludes that the staff is keeping the newspapers from the patients. And when a staff member is initially chatty then later shuns Dr. Rosenhan, he concludes that the man initially mistook him for a psychiatrist because he looks professorial. Both Ms. Cahalan and Dr. Rosenhan approach psychiatry with biases, and they don’t always question their assumptions.
, a professor who didn’t treat patients. This intermixing of the two fields felt contrived to me, and gave too much credence to the idea that no one really knows sane from disordered, and everyone was embracing the antipsychiatry dogma. Surely, someone during the those years must have liked their psychiatrist.
That said, Ms. Cahalan does a phenomenal job of infiltrating the world of the late Dr. Rosenhan. She starts out enamored by him and by his finding that psychiatrists can’t tell real illness from faked disorder. She meets with his friends, his son, his colleagues, his students, and she flies all over the country to meet with those who can help her understand him. She gains access to his personal files and to the book he started to write about the experiment, then abandoned, which eventually resulted in a lawsuit by Doubleday to have the book’s advance returned. At one point, she even hires a private detective.
What is Ms. Cahalan looking for so desperately? She’s looking for these anonymous pseudopatients, the people who were admitted to these unnamed state hospitals, who made observations and took notes, who were diagnosed with schizophrenia and then finally released. She’s looking for the truth, and while she identifies Dr. Rosenhan and two other pseudopatients as people who faked their way into the hospital, she finds a mass of contradictions. The one pseudopatient was excluded from the study – he is the one who felt comforted by his time in the hospital. The other six pseudopatients could not be found, despite Ms. Cahalan’s heroic attempts. Furthermore, she found many inconsistencies in what Dr. Rosenhan reported, and his hospital notes revealed more than a presentation for voices saying “empty, hollow, thud.” He reported it had been going on for months, that he had put copper over his ears to block the sound, and that he felt suicidal.
Ultimately, Ms. Cahalan was left to conclude that the Rosenhan experiment was a lie, that the pseudopatients likely never existed and the article was a fabrication. She brings up other studies that have been proven to be fraudulent, and by this point, our faith in all of science is pretty shaken.
Ms. Cahalan took a long journey to get us to this place, one that spent a lot of effort in bashing psychiatry, finally concluding that, as a result of this fraudulent experiment, too many hospitals have been shuttered – leaving our sickest patients to the streets and to the jails – and that there are not enough mental health professionals. As a psychiatrist – one who is often willing to question our practices – I was distracted by the flagrant antipsychiatry sentiments. Reading past that, Ms. Cahalan’s remarkable detective work and creative intermingling of the Rosenhan experiment layered on the history of psychiatry, further layered on her own experience with psychosis, makes for an amazing story. The Rosenhan study may have rocked the world of psychiatry; the fact that it was fabricated should rock us even more.
Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.
As an undergraduate psychology major, I was taught about the Rosenhan study in several of my courses. My professors lectured about the shocking findings psychologist David Rosenhan, PhD, documented in a 1973 Science article, “On Being Sane in Insane Places” and these findings lent themselves to lecture hall drama. Eight people presented to hospitals and said they heard voices saying: “empty, hollow, thud.” These “pseudopatients” exhibited no other psychiatric symptoms but were admitted, diagnosed with schizophrenia, and observations of their behavior were made. The charts included notes such as, “Patient exhibits writing behavior,” my professors said. The pseudopatients were kept for an average of 19 days, and one for as long as 51 days. The decades have passed, and there are many things I learned in college that I have since forgotten, but I remember “empty, hollow, thud,” and the famous Rosenhan experiment.
I was eager to read Susannah Cahalan’s book, “The Great Pretender” (Grand Central Publishing, 2019), which puts both Dr. Rosenhan and his pseudopatient study under a microscope. Ms. Cahalan is the author of the page-turner, Brain on Fire: My Month of Madness (Free Press, 2012), where she recounted her own struggle with a psychotic episode. Ms. Cahalan, a young reporter in New York City, became psychotic and then catatonic; her condition perplexed the neurologists who were treating her on an inpatient unit, and they were on the verge of transferring her to psychiatry when a diagnosis of anti-NMDA receptor encephalitis was suspected and then confirmed with a brain biopsy. Ms. Cahalan made a full recovery after treatment with steroids, intravenous immunoglobulin, and plasmapheresis. While Ms. Cahalan’s symptoms were classic for a severe psychotic disorder, there was reason to believe that this was not a primary psychiatric disorder: She was having grand mal seizures. Her book was a bestseller, and she has spoken widely to make others aware of this rare illness that masquerades as psychosis. I heard her speak at the opening session of the American Psychiatric Association’s annual meeting in May of 2017.“My family, like many families before them, fought against the tyranny of the mental illness label,” Ms. Cahalan writes at the very beginning of “The Great Pretender.” She goes on to talk about how psychiatry differs from other medical fields: It’s the only specialty where people can be treated against their will; psychiatry casts judgments on the person; mental illness is poorly defined – perhaps there is no clear divide between normal and mad; and psychiatric disorders are less “real” than other illnesses. Throughout the book she refers to psychiatrists as smug and arrogant.
Ms. Cahalan takes on the task of documenting the horrors of psychiatry’s often sordid history, starting with journalist Nellie Bly’s 1887 journey into to a psychiatric facility to expose the abuses there. Certainly, psychiatry’s history is sordid. Ms. Cahalan talks about inhumane conditions in overcrowded psychiatric hospitals, about our sad chapter of lobotomies, about the influence of psychoanalysis on diagnosis and treatment, and about how homosexuality was once an illness and now is not. She includes “One Flew Over the Cuckoo’s Nest,” “The Myth of Mental Illness,” big pharma, and the Goldwater fiasco. In her recounting of the history, it’s all bad. She mentions Benjamin Rush, MD, only once, as the creator of “ ‘... the tranquilizing chair’ (a case of the worst false advertising ever), a terrifying sensory-deprivation apparatus in which patients were strapped down to a chair with a wooden box placed over their heads to block stimulation, restrict movement, and reduce blood to the brain.” Dr. Rush’s role as the father of American psychiatry who challenged the belief that mental illness was the result of demonic possession, gets no mention. Nor does Ms. Cahalan note that he founded Pennsylvania Hospital, where moral and occupational therapy revolutionized the treatment of those with mental illness.
So there’s her story, her rendition of the history of American psychiatry, and through this she weaves in the story of the Rosenhan experiment.
“ ‘It all started out as a dare,’ Dr. Rosenhan told a local newspaper, ‘I was teaching psychology at Swarthmore, and my students were saying that the course was too conceptual and abstract. So I said, ‘Okay, if you really want to know what mental patients are like, become mental patients.’ ”
Really? I read this and wondered how a psychologist could talk about people who had been hospitalized with psychiatric disorders as though they were aliens. Certainly, some of these students, their family members, or their friends must have been hospitalized at some point. Yet all through, there is this sense that the patients are other, and the discovery of the undercover operation is that the patients are actually human beings! Dr. Rosenhan, who was one of the pseudopatients, goes on to conclude that the label is everything, that once labeled they are treated differently by the nurses in “cages” and the doctors who walk by and avert their gaze. A second man Ms. Cahalan named, also one of the pseudopatients, had a similar experience. A third subject she located was not included in the study: His experience was counter to the findings of the study, his time in the hospital was a positive, he found it comforting, and the experiences he had there had a lasting positive influence on his life.
Ms. Cahalan talks about the publication of “On Being Sane in Insane Places” as a study that was finally scientific, one that changed all of psychiatry, and was the driving force for the creation of the DSM-III and the closure of state hospitals. I wondered if it was as influential as Ms. Cahalan claims, and I asked some psychiatrists who were practicing in 1973 when the article was published. I wanted to know if this study rocked their world.
“At first, with the great amount of publicity the study generated, it was added fodder for the antipsychiatrists, including the Scientologists and Szaszians,” Steven Sharfstein, MD, a former president of the American Psychiatric Association, told me. “But as young psychiatrists in the trenches, business continued to boom, and we continued to do the best job we could with diagnosis, assessment of risk, involuntary commitment, and treatment. And from what I recall, morale was high in the 1970s. We had some new medications and psychotherapies, and there was community activism. Faking symptoms to gain admission seemed to be a no-brainer, but keeping people for long stays was more problematic.”
E. Fuller Torrey, MD, the founder of the Treatment Advocacy Center who worked for many years treating patients at St. Elizabeth’s Hospital, replied: “It is important to remember that this study was published at the height of the deinstitutionalization movement and quite likely accelerated it. As I recall, at the time it seemed odd that all eight patients claimed to have had similar experiences while hospitalized. I think the main effect of the study was to provide ammunition for the antipsychiatrists.”
Ms. Cahalan has bought into the antipsychiatry movement full force. It’s not until the very end that there is any acknowledgment that psychiatry ever helped anyone, and even then, it’s a bit begrudging. Worse, she neglects to mention that people with psychiatric disorders suffer because of their psychic pain; one could get through this book and believe that people with mental illness struggle only because they are labeled and then mistreated, and for someone who has suffered herself, she misses the essence of how awful it is to be ill, and that people are often helped by psychiatric treatments. When she finally adds a paragraph talking about the usefulness of psychotropics, it’s with a caveat. “But I’m not here to rail against the drugs. There are plenty of places you can get that perspective. I see that these drugs help many people lead full and meaningful lives. It would be folly to discount their worth. We also can’t deny that the situation is complicated.”
There are moments in the manuscript where I found it difficult to know what were Dr. Rosenhan’s interpretations and what were Ms. Callahan’s interpretations of Dr. Rosenhan’s experiences. A lot of assumptions are made – particularly about the motivations of the hospital staff – and I wasn’t always sure they were correct. For example, on his second day in the hospital, Dr. Rosenhan asked a nurse for the newspaper. When she tells him it hasn’t come yet, he concludes that the staff is keeping the newspapers from the patients. And when a staff member is initially chatty then later shuns Dr. Rosenhan, he concludes that the man initially mistook him for a psychiatrist because he looks professorial. Both Ms. Cahalan and Dr. Rosenhan approach psychiatry with biases, and they don’t always question their assumptions.
, a professor who didn’t treat patients. This intermixing of the two fields felt contrived to me, and gave too much credence to the idea that no one really knows sane from disordered, and everyone was embracing the antipsychiatry dogma. Surely, someone during the those years must have liked their psychiatrist.
That said, Ms. Cahalan does a phenomenal job of infiltrating the world of the late Dr. Rosenhan. She starts out enamored by him and by his finding that psychiatrists can’t tell real illness from faked disorder. She meets with his friends, his son, his colleagues, his students, and she flies all over the country to meet with those who can help her understand him. She gains access to his personal files and to the book he started to write about the experiment, then abandoned, which eventually resulted in a lawsuit by Doubleday to have the book’s advance returned. At one point, she even hires a private detective.
What is Ms. Cahalan looking for so desperately? She’s looking for these anonymous pseudopatients, the people who were admitted to these unnamed state hospitals, who made observations and took notes, who were diagnosed with schizophrenia and then finally released. She’s looking for the truth, and while she identifies Dr. Rosenhan and two other pseudopatients as people who faked their way into the hospital, she finds a mass of contradictions. The one pseudopatient was excluded from the study – he is the one who felt comforted by his time in the hospital. The other six pseudopatients could not be found, despite Ms. Cahalan’s heroic attempts. Furthermore, she found many inconsistencies in what Dr. Rosenhan reported, and his hospital notes revealed more than a presentation for voices saying “empty, hollow, thud.” He reported it had been going on for months, that he had put copper over his ears to block the sound, and that he felt suicidal.
Ultimately, Ms. Cahalan was left to conclude that the Rosenhan experiment was a lie, that the pseudopatients likely never existed and the article was a fabrication. She brings up other studies that have been proven to be fraudulent, and by this point, our faith in all of science is pretty shaken.
Ms. Cahalan took a long journey to get us to this place, one that spent a lot of effort in bashing psychiatry, finally concluding that, as a result of this fraudulent experiment, too many hospitals have been shuttered – leaving our sickest patients to the streets and to the jails – and that there are not enough mental health professionals. As a psychiatrist – one who is often willing to question our practices – I was distracted by the flagrant antipsychiatry sentiments. Reading past that, Ms. Cahalan’s remarkable detective work and creative intermingling of the Rosenhan experiment layered on the history of psychiatry, further layered on her own experience with psychosis, makes for an amazing story. The Rosenhan study may have rocked the world of psychiatry; the fact that it was fabricated should rock us even more.
Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.
Patients need physicians who see – and feel – beyond the EMR
CHICAGO – Speaking to a rapt audience of radiologists, an infectious disease physician who writes and teaches about the importance of human touch in medicine held sway at the opening session of the annual meeting of the Radiological Society of North America.
It wasn’t hard for Abraham Verghese, MD, to find points of commonality between those who sit in dark reading rooms and those who roam the wards.
The EMR, Dr. Verghese said, is a “system of epic disaster. It was not designed for ease of use; it was designed for billing. ... Frankly, we are the highest-paid clerical workers in the hospital, and that has to change. The Stone Age didn’t end because we ran out of stone; it ended because we had better ideas.”
The daily EMR click count for physicians has been estimated at 4,000, and it’s but part of the problem, said Dr. Verghese, professor of medicine at Stanford (Calif.) University. “For every hour of cumulative patient care, physicians spend 1½ hours on the computer, and another hour of our personal time at home dealing with our inbox,” he said. EMR systems may dominate clinical life for physicians, “but they were not built for our ease.”
Dr. Verghese is a practicing physician and medical educator, and is also the author of a body of fiction and nonfiction literature that delineates the physician-patient relationship. His TED-style talk followed opening remarks from Valerie Jackson, MD, the president of the Radiological Society of North America, who encouraged radiologists to reach out for a more direct connection with patients and with nonradiologist colleagues.
The patient connection – the human factor that leads many into the practice of medicine – can be eroded for myriad reasons, but health care systems that don’t elevate the physician-patient relationship do so at the peril of serious physician burnout, said Dr. Verghese. By some measures, and in some specialties, half of physicians score high on validated burnout indices – and a burned-out physician is at high risk for leaving the profession.
Dr. Verghese quoted the poet Anatole Broyard, who was treated for prostate cancer and wrote extensively about his experiences.
Wishing for a more personal connection with his physician, Mr. Broyard wrote: “I just wish he would brood on my situation for perhaps 5 minutes, that he would give me his whole mind just once, be bonded with me for a brief space, survey my soul as well as my flesh, to get at my illness, for each man is ill in his own way.”
It’s this opportunity for connection and contemplation that is sacrificed when, as Dr. Verghese said, “the patient in the bed has become a mere icon for the ‘real’ patient in the computer.”
Dr. Jackson, executive director of the American Board of Radiology, and Dr. Verghese both acknowledged that authentic patient connections can make practice more rewarding and reduce the risk of burnout.
Dr. Verghese also discussed other areas of risk when patients and their physicians are separated by an electronic divide.
“We are all getting distracted by our peripheral brains,” and patients may suffer when medical errors result from inattention and a reluctance to “trust what our eyes are showing us,” he said. He and his colleagues solicited and reported 208 vignettes of medical error. In 63% of the cases, the root cause of the error was failure to perform a physical examination (Am J Med. 2015 Dec;128[12]:1322-4.e3). “Patients have a front side – and a back side!” he said, to appreciative laughter. A careful physical exam, he said, involves inspecting – and palpating – both sides.
The act of putting hands on an unclothed patient for a physical exam would violate many societal norms, said Dr. Verghese, were it not for the special rules conferred on the physician-patient relationship.
“One individual in this dyad disrobes and allows touch. In any other context in this society, this is assault,” he said. “The very great privilege of our profession ... is that we are privileged to examine [patients’] bodies, and to touch.”
The gift of this ritual is not to be squandered, he said, adding that patients understand the special rhythm of the physical examination. “If you come in and do a half-assed probe of their belly and stick your stethoscope on top of their paper gown, they are on to you.”
Describing his own method for the physical exam, Dr. Verghese said that there’s something that feels commandeering and intrusive about beginning directly at the head, as one is taught. Instead, he offers an outstretched hand and begins with a handshake, noting grip strength, any tremor, hydration, and condition of skin and nails. Then, he caps the handshake with his other hand and slides two fingers over to the radial pulse, where he gathers more information, all the while strengthening his bond with his patient. His exam, he said, is his own, with its own rhythms and order which have not varied in decades.
Whatever the method, “this skill has to be passed on, and there is no easy way to do it. ... But when you examine well, you are preserving the ‘person-ality,’ the embodied identity of the patient.”
From the time of William Osler – and perhaps before – the physical examination has been a “symbolic centering on the body as a locus of personhood and disease,” said Dr. Verghese.
Dr. Jackson encouraged her radiologist peers to come out from the reading room to greet and connect with patients in the imaging suite. Similarly, Dr. Verghese said, technology can be used to “connect the image, or the biopsy report, or the lab test, to the personhood” of the patient. Bringing a tablet with imaging results or a laboratory readout to the bedside or the exam table and helping the patient place the findings on or within her own body marries the best of old and new.
He shared with the audience his practice for examining patients presenting with chronic fatigue – a condition that can be challenging to diagnose and manage.
These patients “come to you ready for you to join the long line of physicians who have disappointed them,” said Dr. Verghese, who at one time saw many such patients. He said that he developed a strategy of first listening, and then examining. “A very interesting thing happened – the voluble patient began to quiet down” under his examiner’s hands. If patients could, through his approach, relinquish their ceaseless quest for a definitive diagnosis “and instead begin a partnership toward wellness,” he felt he’d reached success. “It was because something magical had transpired in that encounter.”
Neither Dr. Verghese nor Dr. Jackson reported any conflicts of interest relevant to their presentations.
CHICAGO – Speaking to a rapt audience of radiologists, an infectious disease physician who writes and teaches about the importance of human touch in medicine held sway at the opening session of the annual meeting of the Radiological Society of North America.
It wasn’t hard for Abraham Verghese, MD, to find points of commonality between those who sit in dark reading rooms and those who roam the wards.
The EMR, Dr. Verghese said, is a “system of epic disaster. It was not designed for ease of use; it was designed for billing. ... Frankly, we are the highest-paid clerical workers in the hospital, and that has to change. The Stone Age didn’t end because we ran out of stone; it ended because we had better ideas.”
The daily EMR click count for physicians has been estimated at 4,000, and it’s but part of the problem, said Dr. Verghese, professor of medicine at Stanford (Calif.) University. “For every hour of cumulative patient care, physicians spend 1½ hours on the computer, and another hour of our personal time at home dealing with our inbox,” he said. EMR systems may dominate clinical life for physicians, “but they were not built for our ease.”
Dr. Verghese is a practicing physician and medical educator, and is also the author of a body of fiction and nonfiction literature that delineates the physician-patient relationship. His TED-style talk followed opening remarks from Valerie Jackson, MD, the president of the Radiological Society of North America, who encouraged radiologists to reach out for a more direct connection with patients and with nonradiologist colleagues.
The patient connection – the human factor that leads many into the practice of medicine – can be eroded for myriad reasons, but health care systems that don’t elevate the physician-patient relationship do so at the peril of serious physician burnout, said Dr. Verghese. By some measures, and in some specialties, half of physicians score high on validated burnout indices – and a burned-out physician is at high risk for leaving the profession.
Dr. Verghese quoted the poet Anatole Broyard, who was treated for prostate cancer and wrote extensively about his experiences.
Wishing for a more personal connection with his physician, Mr. Broyard wrote: “I just wish he would brood on my situation for perhaps 5 minutes, that he would give me his whole mind just once, be bonded with me for a brief space, survey my soul as well as my flesh, to get at my illness, for each man is ill in his own way.”
It’s this opportunity for connection and contemplation that is sacrificed when, as Dr. Verghese said, “the patient in the bed has become a mere icon for the ‘real’ patient in the computer.”
Dr. Jackson, executive director of the American Board of Radiology, and Dr. Verghese both acknowledged that authentic patient connections can make practice more rewarding and reduce the risk of burnout.
Dr. Verghese also discussed other areas of risk when patients and their physicians are separated by an electronic divide.
“We are all getting distracted by our peripheral brains,” and patients may suffer when medical errors result from inattention and a reluctance to “trust what our eyes are showing us,” he said. He and his colleagues solicited and reported 208 vignettes of medical error. In 63% of the cases, the root cause of the error was failure to perform a physical examination (Am J Med. 2015 Dec;128[12]:1322-4.e3). “Patients have a front side – and a back side!” he said, to appreciative laughter. A careful physical exam, he said, involves inspecting – and palpating – both sides.
The act of putting hands on an unclothed patient for a physical exam would violate many societal norms, said Dr. Verghese, were it not for the special rules conferred on the physician-patient relationship.
“One individual in this dyad disrobes and allows touch. In any other context in this society, this is assault,” he said. “The very great privilege of our profession ... is that we are privileged to examine [patients’] bodies, and to touch.”
The gift of this ritual is not to be squandered, he said, adding that patients understand the special rhythm of the physical examination. “If you come in and do a half-assed probe of their belly and stick your stethoscope on top of their paper gown, they are on to you.”
Describing his own method for the physical exam, Dr. Verghese said that there’s something that feels commandeering and intrusive about beginning directly at the head, as one is taught. Instead, he offers an outstretched hand and begins with a handshake, noting grip strength, any tremor, hydration, and condition of skin and nails. Then, he caps the handshake with his other hand and slides two fingers over to the radial pulse, where he gathers more information, all the while strengthening his bond with his patient. His exam, he said, is his own, with its own rhythms and order which have not varied in decades.
Whatever the method, “this skill has to be passed on, and there is no easy way to do it. ... But when you examine well, you are preserving the ‘person-ality,’ the embodied identity of the patient.”
From the time of William Osler – and perhaps before – the physical examination has been a “symbolic centering on the body as a locus of personhood and disease,” said Dr. Verghese.
Dr. Jackson encouraged her radiologist peers to come out from the reading room to greet and connect with patients in the imaging suite. Similarly, Dr. Verghese said, technology can be used to “connect the image, or the biopsy report, or the lab test, to the personhood” of the patient. Bringing a tablet with imaging results or a laboratory readout to the bedside or the exam table and helping the patient place the findings on or within her own body marries the best of old and new.
He shared with the audience his practice for examining patients presenting with chronic fatigue – a condition that can be challenging to diagnose and manage.
These patients “come to you ready for you to join the long line of physicians who have disappointed them,” said Dr. Verghese, who at one time saw many such patients. He said that he developed a strategy of first listening, and then examining. “A very interesting thing happened – the voluble patient began to quiet down” under his examiner’s hands. If patients could, through his approach, relinquish their ceaseless quest for a definitive diagnosis “and instead begin a partnership toward wellness,” he felt he’d reached success. “It was because something magical had transpired in that encounter.”
Neither Dr. Verghese nor Dr. Jackson reported any conflicts of interest relevant to their presentations.
CHICAGO – Speaking to a rapt audience of radiologists, an infectious disease physician who writes and teaches about the importance of human touch in medicine held sway at the opening session of the annual meeting of the Radiological Society of North America.
It wasn’t hard for Abraham Verghese, MD, to find points of commonality between those who sit in dark reading rooms and those who roam the wards.
The EMR, Dr. Verghese said, is a “system of epic disaster. It was not designed for ease of use; it was designed for billing. ... Frankly, we are the highest-paid clerical workers in the hospital, and that has to change. The Stone Age didn’t end because we ran out of stone; it ended because we had better ideas.”
The daily EMR click count for physicians has been estimated at 4,000, and it’s but part of the problem, said Dr. Verghese, professor of medicine at Stanford (Calif.) University. “For every hour of cumulative patient care, physicians spend 1½ hours on the computer, and another hour of our personal time at home dealing with our inbox,” he said. EMR systems may dominate clinical life for physicians, “but they were not built for our ease.”
Dr. Verghese is a practicing physician and medical educator, and is also the author of a body of fiction and nonfiction literature that delineates the physician-patient relationship. His TED-style talk followed opening remarks from Valerie Jackson, MD, the president of the Radiological Society of North America, who encouraged radiologists to reach out for a more direct connection with patients and with nonradiologist colleagues.
The patient connection – the human factor that leads many into the practice of medicine – can be eroded for myriad reasons, but health care systems that don’t elevate the physician-patient relationship do so at the peril of serious physician burnout, said Dr. Verghese. By some measures, and in some specialties, half of physicians score high on validated burnout indices – and a burned-out physician is at high risk for leaving the profession.
Dr. Verghese quoted the poet Anatole Broyard, who was treated for prostate cancer and wrote extensively about his experiences.
Wishing for a more personal connection with his physician, Mr. Broyard wrote: “I just wish he would brood on my situation for perhaps 5 minutes, that he would give me his whole mind just once, be bonded with me for a brief space, survey my soul as well as my flesh, to get at my illness, for each man is ill in his own way.”
It’s this opportunity for connection and contemplation that is sacrificed when, as Dr. Verghese said, “the patient in the bed has become a mere icon for the ‘real’ patient in the computer.”
Dr. Jackson, executive director of the American Board of Radiology, and Dr. Verghese both acknowledged that authentic patient connections can make practice more rewarding and reduce the risk of burnout.
Dr. Verghese also discussed other areas of risk when patients and their physicians are separated by an electronic divide.
“We are all getting distracted by our peripheral brains,” and patients may suffer when medical errors result from inattention and a reluctance to “trust what our eyes are showing us,” he said. He and his colleagues solicited and reported 208 vignettes of medical error. In 63% of the cases, the root cause of the error was failure to perform a physical examination (Am J Med. 2015 Dec;128[12]:1322-4.e3). “Patients have a front side – and a back side!” he said, to appreciative laughter. A careful physical exam, he said, involves inspecting – and palpating – both sides.
The act of putting hands on an unclothed patient for a physical exam would violate many societal norms, said Dr. Verghese, were it not for the special rules conferred on the physician-patient relationship.
“One individual in this dyad disrobes and allows touch. In any other context in this society, this is assault,” he said. “The very great privilege of our profession ... is that we are privileged to examine [patients’] bodies, and to touch.”
The gift of this ritual is not to be squandered, he said, adding that patients understand the special rhythm of the physical examination. “If you come in and do a half-assed probe of their belly and stick your stethoscope on top of their paper gown, they are on to you.”
Describing his own method for the physical exam, Dr. Verghese said that there’s something that feels commandeering and intrusive about beginning directly at the head, as one is taught. Instead, he offers an outstretched hand and begins with a handshake, noting grip strength, any tremor, hydration, and condition of skin and nails. Then, he caps the handshake with his other hand and slides two fingers over to the radial pulse, where he gathers more information, all the while strengthening his bond with his patient. His exam, he said, is his own, with its own rhythms and order which have not varied in decades.
Whatever the method, “this skill has to be passed on, and there is no easy way to do it. ... But when you examine well, you are preserving the ‘person-ality,’ the embodied identity of the patient.”
From the time of William Osler – and perhaps before – the physical examination has been a “symbolic centering on the body as a locus of personhood and disease,” said Dr. Verghese.
Dr. Jackson encouraged her radiologist peers to come out from the reading room to greet and connect with patients in the imaging suite. Similarly, Dr. Verghese said, technology can be used to “connect the image, or the biopsy report, or the lab test, to the personhood” of the patient. Bringing a tablet with imaging results or a laboratory readout to the bedside or the exam table and helping the patient place the findings on or within her own body marries the best of old and new.
He shared with the audience his practice for examining patients presenting with chronic fatigue – a condition that can be challenging to diagnose and manage.
These patients “come to you ready for you to join the long line of physicians who have disappointed them,” said Dr. Verghese, who at one time saw many such patients. He said that he developed a strategy of first listening, and then examining. “A very interesting thing happened – the voluble patient began to quiet down” under his examiner’s hands. If patients could, through his approach, relinquish their ceaseless quest for a definitive diagnosis “and instead begin a partnership toward wellness,” he felt he’d reached success. “It was because something magical had transpired in that encounter.”
Neither Dr. Verghese nor Dr. Jackson reported any conflicts of interest relevant to their presentations.
EXPERT ANALYSIS FROM RSNA 2019
Capecitabine extends survival in triple-negative breast cancer
SAN ANTONIO – For patients with early-stage triple-negative breast cancer, adding capecitabine to systemic treatment may extend overall survival, according to a meta-analysis involving more than 15,000 patients.
Although a variety of trials have tested capecitabine therapy for early-stage breast cancer, this study is the first to evaluate individual patient data across trials, reported lead author Marion van Mackelenbergh, MD, of University Medical Center Schleswig-Holstein in Kiel, Germany, and colleagues.
According to Dr. Mackelenbergh, who presented findings at the San Antonio Breast Cancer Symposium, the two previous literature-based meta-analyses of capecitabine for patients with early-stage breast cancer reported conflicting results; the first study suggested that capecitabine had no benefit as a neoadjuvant therapy, whereas the second study concluded that capecitabine could improve disease-free survival (DFS).
To build upon these findings, the primary objective of the present meta-analysis was to determine how treatment with capecitabine impacts DFS, Dr. Mackelenbergh said. A variety of secondary objectives were also evaluated, including overall survival and a possible interaction between capecitabine-specific toxicities and treatment effects.
The analysis involved 15,457 patients from 12 randomized prospective clinical trials, of whom about half (n = 7,477) were treated in control arms. Slightly more than half (55.9%) of the patients had stage II tumors and about three-fourths (74.0%) presented with nodal involvement. About two-thirds of patients (66.0%) had estrogen receptor–positive disease, about half (56.9%) were progesterone receptor–positive, and 15.1% were human epidermal growth factor receptor 2–positive. Most of the patients (81.8%) were treated with chemotherapy in the adjuvant setting, whereas the remainder (18.2%) received neoadjuvant therapy.
Cox regression analysis involving all patients in the dataset showed that capecitabine was not associated with a significant improvement in DFS, nor was a significant improvement seen in trials that compared capecitabine against other treatment options. In contrast, adding capecitabine to systemic treatment supported a modest but significant improvement in DFS (hazard ratio, 0.888; P = .0005).
Across all patients, capecitabine was associated with an overall survival advantage, although this benefit was relatively small, with a hazard ratio of 0.892. The overall survival benefit became more pronounced when capecitabine was added to systemic treatment (HR, 0.837).
Of clinical importance, biological subtype analysis showed that only patients with triple-negative breast cancer were deriving survival benefit from capecitabine, particularly when capecitabine was added to systemic treatment. Among patients with triple-negative disease, a 17% overall survival benefit was associated with capecitabine (HR, 0.828). When capecitabine was added to systemic treatment, this survival advantage improved to 22% (HR, 0.778).
No relationship was found between capecitabine-specific toxicity (mucositis, hand-foot syndrome, diarrhea) and patient outcome.
“It can be concluded that the addition of capecitabine to other systemic treatment may be recommended for triple-negative breast cancer patients,” Dr. Mackelenbergh said.
Invited discussant Priyanka Sharma, MD, of the University of Kansas Medical Center in Kansas City agreed with this conclusion.
“Routine use of capecitabine as a component of neoadjuvant or adjuvant regimens in unselected patients cannot be endorsed,” Dr. Sharma said. “However, capecitabine should be considered in patients with triple-negative breast cancer, especially if response to neoadjuvant chemotherapy is utilized as a way to identify eligible patients so as to limit exposure and toxicity to those at the highest risk.”
In terms of the future, Dr. Sharma suggested that research is needed to determine the potential for adjuvant capecitabine among patients with triple-negative breast cancer who have received platinum-based chemotherapy and/or immune checkpoint inhibitor therapy as part of their neoadjuvant regimen. In addition, investigators should evaluate capecitabine efficacy in terms of residual disease and identify relevant predictive biomarkers, Dr. Sharma said.
The investigators reported relationships with Amgen, Lilly, Pfizer, and others.
SOURCE: van Mackelenbergh M et al. SABCS 2019, Abstract GS1-07.
SAN ANTONIO – For patients with early-stage triple-negative breast cancer, adding capecitabine to systemic treatment may extend overall survival, according to a meta-analysis involving more than 15,000 patients.
Although a variety of trials have tested capecitabine therapy for early-stage breast cancer, this study is the first to evaluate individual patient data across trials, reported lead author Marion van Mackelenbergh, MD, of University Medical Center Schleswig-Holstein in Kiel, Germany, and colleagues.
According to Dr. Mackelenbergh, who presented findings at the San Antonio Breast Cancer Symposium, the two previous literature-based meta-analyses of capecitabine for patients with early-stage breast cancer reported conflicting results; the first study suggested that capecitabine had no benefit as a neoadjuvant therapy, whereas the second study concluded that capecitabine could improve disease-free survival (DFS).
To build upon these findings, the primary objective of the present meta-analysis was to determine how treatment with capecitabine impacts DFS, Dr. Mackelenbergh said. A variety of secondary objectives were also evaluated, including overall survival and a possible interaction between capecitabine-specific toxicities and treatment effects.
The analysis involved 15,457 patients from 12 randomized prospective clinical trials, of whom about half (n = 7,477) were treated in control arms. Slightly more than half (55.9%) of the patients had stage II tumors and about three-fourths (74.0%) presented with nodal involvement. About two-thirds of patients (66.0%) had estrogen receptor–positive disease, about half (56.9%) were progesterone receptor–positive, and 15.1% were human epidermal growth factor receptor 2–positive. Most of the patients (81.8%) were treated with chemotherapy in the adjuvant setting, whereas the remainder (18.2%) received neoadjuvant therapy.
Cox regression analysis involving all patients in the dataset showed that capecitabine was not associated with a significant improvement in DFS, nor was a significant improvement seen in trials that compared capecitabine against other treatment options. In contrast, adding capecitabine to systemic treatment supported a modest but significant improvement in DFS (hazard ratio, 0.888; P = .0005).
Across all patients, capecitabine was associated with an overall survival advantage, although this benefit was relatively small, with a hazard ratio of 0.892. The overall survival benefit became more pronounced when capecitabine was added to systemic treatment (HR, 0.837).
Of clinical importance, biological subtype analysis showed that only patients with triple-negative breast cancer were deriving survival benefit from capecitabine, particularly when capecitabine was added to systemic treatment. Among patients with triple-negative disease, a 17% overall survival benefit was associated with capecitabine (HR, 0.828). When capecitabine was added to systemic treatment, this survival advantage improved to 22% (HR, 0.778).
No relationship was found between capecitabine-specific toxicity (mucositis, hand-foot syndrome, diarrhea) and patient outcome.
“It can be concluded that the addition of capecitabine to other systemic treatment may be recommended for triple-negative breast cancer patients,” Dr. Mackelenbergh said.
Invited discussant Priyanka Sharma, MD, of the University of Kansas Medical Center in Kansas City agreed with this conclusion.
“Routine use of capecitabine as a component of neoadjuvant or adjuvant regimens in unselected patients cannot be endorsed,” Dr. Sharma said. “However, capecitabine should be considered in patients with triple-negative breast cancer, especially if response to neoadjuvant chemotherapy is utilized as a way to identify eligible patients so as to limit exposure and toxicity to those at the highest risk.”
In terms of the future, Dr. Sharma suggested that research is needed to determine the potential for adjuvant capecitabine among patients with triple-negative breast cancer who have received platinum-based chemotherapy and/or immune checkpoint inhibitor therapy as part of their neoadjuvant regimen. In addition, investigators should evaluate capecitabine efficacy in terms of residual disease and identify relevant predictive biomarkers, Dr. Sharma said.
The investigators reported relationships with Amgen, Lilly, Pfizer, and others.
SOURCE: van Mackelenbergh M et al. SABCS 2019, Abstract GS1-07.
SAN ANTONIO – For patients with early-stage triple-negative breast cancer, adding capecitabine to systemic treatment may extend overall survival, according to a meta-analysis involving more than 15,000 patients.
Although a variety of trials have tested capecitabine therapy for early-stage breast cancer, this study is the first to evaluate individual patient data across trials, reported lead author Marion van Mackelenbergh, MD, of University Medical Center Schleswig-Holstein in Kiel, Germany, and colleagues.
According to Dr. Mackelenbergh, who presented findings at the San Antonio Breast Cancer Symposium, the two previous literature-based meta-analyses of capecitabine for patients with early-stage breast cancer reported conflicting results; the first study suggested that capecitabine had no benefit as a neoadjuvant therapy, whereas the second study concluded that capecitabine could improve disease-free survival (DFS).
To build upon these findings, the primary objective of the present meta-analysis was to determine how treatment with capecitabine impacts DFS, Dr. Mackelenbergh said. A variety of secondary objectives were also evaluated, including overall survival and a possible interaction between capecitabine-specific toxicities and treatment effects.
The analysis involved 15,457 patients from 12 randomized prospective clinical trials, of whom about half (n = 7,477) were treated in control arms. Slightly more than half (55.9%) of the patients had stage II tumors and about three-fourths (74.0%) presented with nodal involvement. About two-thirds of patients (66.0%) had estrogen receptor–positive disease, about half (56.9%) were progesterone receptor–positive, and 15.1% were human epidermal growth factor receptor 2–positive. Most of the patients (81.8%) were treated with chemotherapy in the adjuvant setting, whereas the remainder (18.2%) received neoadjuvant therapy.
Cox regression analysis involving all patients in the dataset showed that capecitabine was not associated with a significant improvement in DFS, nor was a significant improvement seen in trials that compared capecitabine against other treatment options. In contrast, adding capecitabine to systemic treatment supported a modest but significant improvement in DFS (hazard ratio, 0.888; P = .0005).
Across all patients, capecitabine was associated with an overall survival advantage, although this benefit was relatively small, with a hazard ratio of 0.892. The overall survival benefit became more pronounced when capecitabine was added to systemic treatment (HR, 0.837).
Of clinical importance, biological subtype analysis showed that only patients with triple-negative breast cancer were deriving survival benefit from capecitabine, particularly when capecitabine was added to systemic treatment. Among patients with triple-negative disease, a 17% overall survival benefit was associated with capecitabine (HR, 0.828). When capecitabine was added to systemic treatment, this survival advantage improved to 22% (HR, 0.778).
No relationship was found between capecitabine-specific toxicity (mucositis, hand-foot syndrome, diarrhea) and patient outcome.
“It can be concluded that the addition of capecitabine to other systemic treatment may be recommended for triple-negative breast cancer patients,” Dr. Mackelenbergh said.
Invited discussant Priyanka Sharma, MD, of the University of Kansas Medical Center in Kansas City agreed with this conclusion.
“Routine use of capecitabine as a component of neoadjuvant or adjuvant regimens in unselected patients cannot be endorsed,” Dr. Sharma said. “However, capecitabine should be considered in patients with triple-negative breast cancer, especially if response to neoadjuvant chemotherapy is utilized as a way to identify eligible patients so as to limit exposure and toxicity to those at the highest risk.”
In terms of the future, Dr. Sharma suggested that research is needed to determine the potential for adjuvant capecitabine among patients with triple-negative breast cancer who have received platinum-based chemotherapy and/or immune checkpoint inhibitor therapy as part of their neoadjuvant regimen. In addition, investigators should evaluate capecitabine efficacy in terms of residual disease and identify relevant predictive biomarkers, Dr. Sharma said.
The investigators reported relationships with Amgen, Lilly, Pfizer, and others.
SOURCE: van Mackelenbergh M et al. SABCS 2019, Abstract GS1-07.
REPORTING FROM SABCS 2019
Evidence builds for effects of obesity, low physical activity on development of psoriatic arthritis
A new Norwegian study has identified a high body mass index and lower levels of physical activity as modifiable risk factors for developing psoriatic arthritis (PsA).
“Our study adds to the growing evidence that the risk of PsA is modifiable and highlights the importance of preventive work against obesity as well as encouraging physical activity in order to reduce the incidence of PsA,” wrote Ruth S. Thomsen, MD, of the Norwegian University of Science and Technology, and coauthors. The study was published in Arthritis Care & Research.
To determine the impact that adiposity and body fat distribution have on developing PsA, the researchers analyzed data from 36,626 women and men who participated in two surveys from the longitudinal, population-based Norwegian HUNT Study. All participants did not have diagnosed PsA at baseline in 1995-1997. Variables used in statistical analysis included calculated baseline BMI, waist circumference, waist-hip ratio, and level of physical activity.
Between baseline and follow-up in 2012, 185 new cases of PsA were reported. One standard deviation increase in BMI (4.2 kg/m2 for women, 3.5 kg/m2 for men) and waist circumstance (10.8 cm for women, 8.6 cm for men) was associated with adjusted hazard ratios of 1.40 (95% confidence interval, 1.24-1.58) and 1.48 (95% CI, 1.31-1.68), accordingly. Obese individuals – defined as BMI of 30 kg/m2 or higher – had an adjusted HR of 2.46 (95% CI, 1.65-3.68) when compared with individuals at normal weight.
Compared to individuals with BMI less than 25 kg/m2 and a high level of physical activity, individuals with BMI at 25 kg/m2 or higher and any lower level of physical activity had an adjusted HR of 2.06 (95% CI, 1.18-3.58). In addition, individuals with a high waist circumference – defined as 81 cm or more in women and 95 cm or more in men – and low physical activity had an adjusted HR of 2.22 (95% CI, 1.37-3.58) in comparison to those with a high waist circumference and high physical activity (adjusted HR, 1.84; 95% CI, 0.97-3.47). Physical activity level was considered low with less than 3 hours of light physical activity and no hard physical activity per week and high with any amount of light activity plus 1 or more hours of hard physical activity.
The authors acknowledged the study’s potential limitations, including the requirement for participants to complete the final two HUNT study surveys and the use of stricter criteria than usual in validating PsA diagnoses.
The study was partially funded by a grant Dr. Thomsen received from the Norwegian Extra Foundation for Health and Rehabilitation. The authors reported no conflicts of interest.
SOURCE: Thomsen RS et al. Arthritis Care Res. 2019 Dec 7. doi: 10.1002/acr.24121.
A new Norwegian study has identified a high body mass index and lower levels of physical activity as modifiable risk factors for developing psoriatic arthritis (PsA).
“Our study adds to the growing evidence that the risk of PsA is modifiable and highlights the importance of preventive work against obesity as well as encouraging physical activity in order to reduce the incidence of PsA,” wrote Ruth S. Thomsen, MD, of the Norwegian University of Science and Technology, and coauthors. The study was published in Arthritis Care & Research.
To determine the impact that adiposity and body fat distribution have on developing PsA, the researchers analyzed data from 36,626 women and men who participated in two surveys from the longitudinal, population-based Norwegian HUNT Study. All participants did not have diagnosed PsA at baseline in 1995-1997. Variables used in statistical analysis included calculated baseline BMI, waist circumference, waist-hip ratio, and level of physical activity.
Between baseline and follow-up in 2012, 185 new cases of PsA were reported. One standard deviation increase in BMI (4.2 kg/m2 for women, 3.5 kg/m2 for men) and waist circumstance (10.8 cm for women, 8.6 cm for men) was associated with adjusted hazard ratios of 1.40 (95% confidence interval, 1.24-1.58) and 1.48 (95% CI, 1.31-1.68), accordingly. Obese individuals – defined as BMI of 30 kg/m2 or higher – had an adjusted HR of 2.46 (95% CI, 1.65-3.68) when compared with individuals at normal weight.
Compared to individuals with BMI less than 25 kg/m2 and a high level of physical activity, individuals with BMI at 25 kg/m2 or higher and any lower level of physical activity had an adjusted HR of 2.06 (95% CI, 1.18-3.58). In addition, individuals with a high waist circumference – defined as 81 cm or more in women and 95 cm or more in men – and low physical activity had an adjusted HR of 2.22 (95% CI, 1.37-3.58) in comparison to those with a high waist circumference and high physical activity (adjusted HR, 1.84; 95% CI, 0.97-3.47). Physical activity level was considered low with less than 3 hours of light physical activity and no hard physical activity per week and high with any amount of light activity plus 1 or more hours of hard physical activity.
The authors acknowledged the study’s potential limitations, including the requirement for participants to complete the final two HUNT study surveys and the use of stricter criteria than usual in validating PsA diagnoses.
The study was partially funded by a grant Dr. Thomsen received from the Norwegian Extra Foundation for Health and Rehabilitation. The authors reported no conflicts of interest.
SOURCE: Thomsen RS et al. Arthritis Care Res. 2019 Dec 7. doi: 10.1002/acr.24121.
A new Norwegian study has identified a high body mass index and lower levels of physical activity as modifiable risk factors for developing psoriatic arthritis (PsA).
“Our study adds to the growing evidence that the risk of PsA is modifiable and highlights the importance of preventive work against obesity as well as encouraging physical activity in order to reduce the incidence of PsA,” wrote Ruth S. Thomsen, MD, of the Norwegian University of Science and Technology, and coauthors. The study was published in Arthritis Care & Research.
To determine the impact that adiposity and body fat distribution have on developing PsA, the researchers analyzed data from 36,626 women and men who participated in two surveys from the longitudinal, population-based Norwegian HUNT Study. All participants did not have diagnosed PsA at baseline in 1995-1997. Variables used in statistical analysis included calculated baseline BMI, waist circumference, waist-hip ratio, and level of physical activity.
Between baseline and follow-up in 2012, 185 new cases of PsA were reported. One standard deviation increase in BMI (4.2 kg/m2 for women, 3.5 kg/m2 for men) and waist circumstance (10.8 cm for women, 8.6 cm for men) was associated with adjusted hazard ratios of 1.40 (95% confidence interval, 1.24-1.58) and 1.48 (95% CI, 1.31-1.68), accordingly. Obese individuals – defined as BMI of 30 kg/m2 or higher – had an adjusted HR of 2.46 (95% CI, 1.65-3.68) when compared with individuals at normal weight.
Compared to individuals with BMI less than 25 kg/m2 and a high level of physical activity, individuals with BMI at 25 kg/m2 or higher and any lower level of physical activity had an adjusted HR of 2.06 (95% CI, 1.18-3.58). In addition, individuals with a high waist circumference – defined as 81 cm or more in women and 95 cm or more in men – and low physical activity had an adjusted HR of 2.22 (95% CI, 1.37-3.58) in comparison to those with a high waist circumference and high physical activity (adjusted HR, 1.84; 95% CI, 0.97-3.47). Physical activity level was considered low with less than 3 hours of light physical activity and no hard physical activity per week and high with any amount of light activity plus 1 or more hours of hard physical activity.
The authors acknowledged the study’s potential limitations, including the requirement for participants to complete the final two HUNT study surveys and the use of stricter criteria than usual in validating PsA diagnoses.
The study was partially funded by a grant Dr. Thomsen received from the Norwegian Extra Foundation for Health and Rehabilitation. The authors reported no conflicts of interest.
SOURCE: Thomsen RS et al. Arthritis Care Res. 2019 Dec 7. doi: 10.1002/acr.24121.
FROM ARTHRITIS CARE & RESEARCH
Phase 2 studies show potential of FcRn blockade in primary ITP
ORLANDO – Treatments targeted to the neonatal Fc receptor are showing promise in phase 2 studies in primary immune thrombocytopenia, investigators reported at the annual meeting of the American Society of Hematology.
Encouraging outcomes support the continued phase 3 development of these agents, which are designed to block the neonatal Fc receptor (FcRn) in patients with this IgG-mediated disease.
Blocking FcRN is intended to prevent recycling of IgG, resulting in IgG degradation, according to the authors of studies evaluating rozanolixizumab, a subcutaneously administered monoclonal antibody, and efgartigimod, an intravenously administered antibody fragment, in primary immune thrombocytopenia (ITP).
Rozanolixizumab
Results of the phase 2 study of rozanolixizumab demonstrated that this agent reduced IgG levels and improved platelet counts at all doses tested, according to the investigators, led by Tadeusz Robak, MD, of the department of hematology at the Medical University of Lodz (Poland).
Efficacy endpoints were seen more quickly – by day 8 of treatment – with single subcutaneous infusions at higher doses, according to the researchers.
Headaches of mild to moderate severity were noted at higher doses, and no patients left the study because of adverse events, they reported.
“These safety, tolerability, and efficacy data support phase 3 development of rozanolixizumab in patients with primary ITP,” wrote Dr. Robak and coauthors in the abstract for their study.
A total of 66 adult patients with primary ITP were enrolled and treated with single or multiple subcutaneous doses of rozanolixizumab administered at 1-week intervals.
Baseline characteristics suggested a “difficult-to-treat” patient cohort that had a median ITP duration of nearly 6 years and a median of four prior therapies, including thrombopoietin receptor agonists in about one-third of patients, according to the investigators.
Platelet counts of at least 50 x 109/L were achieved by day 8 in more than half of patients who received single doses of rozanolixizumab at higher dose levels of 15 mg/kg (58.3%) and 20 mg/kg (54.5%), Dr. Robak and colleagues reported.
Mild to moderate headaches were seen in about 40% of patients over an 8-week observation period. There were no serious infections and, of four serious adverse events occurring during the study, none were deemed to be treatment related, according to the investigators.
“People who have primary ITP may experience low platelet count that can put them at risk for severe bleeding, and there are limited options that provide a rapid increase in platelet count to reduce this risk,” Dr. Robak said in an interview. “These data build on the growing body of evidence that suggest targeting the FcRn pathway could have the potential to transform the treatment experience for people with rare IgG autoantibody–mediated diseases such as primary ITP.”
Efgartigimod
Substantial reductions in IgG levels and clinically relevant increases in platelet counts were seen following a 3-week treatment cycle with efgartigimod in patients with treatment-refractory ITP, according to investigator Adrian C. Newland, MB, BCh, of the Royal London Hospital and coinvestigators.
The human IgG1 antibody Fc-fragment, a natural ligand of FcRN, is engineered to have increased affinity to FcRn, while preserving its pH‐dependent binding, according to the investigators.
Efgartigimod treatment was well tolerated and reduced the proportion of patients with bleeding in the phase 2 study presented at ASH 2019.
“This suggests that targeted IgG reduction with efgartigimod is a potential new treatment modality in primary ITP, and warrants evaluation of longer-term treatment in a larger phase 3 study,” the investigators reported in the abstract for their study.
The report described 38 patients randomized to four weekly intravenous infusions of placebo or efgartigimod at one of two dosing levels. Patients had long-standing ITP, with a median 4.8 years disease duration, and all had either failed splenectomy or had inadequate response to prior treatment.
Efgartigimod treatment rapidly reduced total IgG in all patients who received it, with a mean change from baseline of up to 63.7%, according to investigators.
Platelet counts favored the investigational treatment over placebo by several measures. Platelet counts of at least 50 x 109/L on two or more occasions were seen in 46% of efgartigimod-treated patients and 25% of the placebo group; that platelet count was achieved for 10 or more days in 38% and 0% of the efgartigimod and placebo groups, respectively.
Treatment was well tolerated, according to the investigators, who said there were “no dose-related safety observations.” Full results of the phase 2 investigation were published in the American Journal of Hematology, concurrent with the meeting (2019 Dec 10. doi.org/10.1002/ajh.25680).
The study of rozanolixizumab was supported by UCB; Dr. Robak reported disclosures related to UCB (honoraria, research funding), as well as Takeda, Janssen, Amgen, Roche, AbbVie, Gilead, BeiGene, Acerta, and MorphoSys. The study of efgartigimod was supported by argenx; Dr. Newland reported disclosures related to argenx, Novartis, Angle, Amgen, Ono Pharmaceutical, Shionogi, Rigel, and Dova Pharmaceuticals.
SOURCEs: Robak T et al. ASH 2019, Abstract 897; Newland AC et al. ASH 2019, Abstract 895.
ORLANDO – Treatments targeted to the neonatal Fc receptor are showing promise in phase 2 studies in primary immune thrombocytopenia, investigators reported at the annual meeting of the American Society of Hematology.
Encouraging outcomes support the continued phase 3 development of these agents, which are designed to block the neonatal Fc receptor (FcRn) in patients with this IgG-mediated disease.
Blocking FcRN is intended to prevent recycling of IgG, resulting in IgG degradation, according to the authors of studies evaluating rozanolixizumab, a subcutaneously administered monoclonal antibody, and efgartigimod, an intravenously administered antibody fragment, in primary immune thrombocytopenia (ITP).
Rozanolixizumab
Results of the phase 2 study of rozanolixizumab demonstrated that this agent reduced IgG levels and improved platelet counts at all doses tested, according to the investigators, led by Tadeusz Robak, MD, of the department of hematology at the Medical University of Lodz (Poland).
Efficacy endpoints were seen more quickly – by day 8 of treatment – with single subcutaneous infusions at higher doses, according to the researchers.
Headaches of mild to moderate severity were noted at higher doses, and no patients left the study because of adverse events, they reported.
“These safety, tolerability, and efficacy data support phase 3 development of rozanolixizumab in patients with primary ITP,” wrote Dr. Robak and coauthors in the abstract for their study.
A total of 66 adult patients with primary ITP were enrolled and treated with single or multiple subcutaneous doses of rozanolixizumab administered at 1-week intervals.
Baseline characteristics suggested a “difficult-to-treat” patient cohort that had a median ITP duration of nearly 6 years and a median of four prior therapies, including thrombopoietin receptor agonists in about one-third of patients, according to the investigators.
Platelet counts of at least 50 x 109/L were achieved by day 8 in more than half of patients who received single doses of rozanolixizumab at higher dose levels of 15 mg/kg (58.3%) and 20 mg/kg (54.5%), Dr. Robak and colleagues reported.
Mild to moderate headaches were seen in about 40% of patients over an 8-week observation period. There were no serious infections and, of four serious adverse events occurring during the study, none were deemed to be treatment related, according to the investigators.
“People who have primary ITP may experience low platelet count that can put them at risk for severe bleeding, and there are limited options that provide a rapid increase in platelet count to reduce this risk,” Dr. Robak said in an interview. “These data build on the growing body of evidence that suggest targeting the FcRn pathway could have the potential to transform the treatment experience for people with rare IgG autoantibody–mediated diseases such as primary ITP.”
Efgartigimod
Substantial reductions in IgG levels and clinically relevant increases in platelet counts were seen following a 3-week treatment cycle with efgartigimod in patients with treatment-refractory ITP, according to investigator Adrian C. Newland, MB, BCh, of the Royal London Hospital and coinvestigators.
The human IgG1 antibody Fc-fragment, a natural ligand of FcRN, is engineered to have increased affinity to FcRn, while preserving its pH‐dependent binding, according to the investigators.
Efgartigimod treatment was well tolerated and reduced the proportion of patients with bleeding in the phase 2 study presented at ASH 2019.
“This suggests that targeted IgG reduction with efgartigimod is a potential new treatment modality in primary ITP, and warrants evaluation of longer-term treatment in a larger phase 3 study,” the investigators reported in the abstract for their study.
The report described 38 patients randomized to four weekly intravenous infusions of placebo or efgartigimod at one of two dosing levels. Patients had long-standing ITP, with a median 4.8 years disease duration, and all had either failed splenectomy or had inadequate response to prior treatment.
Efgartigimod treatment rapidly reduced total IgG in all patients who received it, with a mean change from baseline of up to 63.7%, according to investigators.
Platelet counts favored the investigational treatment over placebo by several measures. Platelet counts of at least 50 x 109/L on two or more occasions were seen in 46% of efgartigimod-treated patients and 25% of the placebo group; that platelet count was achieved for 10 or more days in 38% and 0% of the efgartigimod and placebo groups, respectively.
Treatment was well tolerated, according to the investigators, who said there were “no dose-related safety observations.” Full results of the phase 2 investigation were published in the American Journal of Hematology, concurrent with the meeting (2019 Dec 10. doi.org/10.1002/ajh.25680).
The study of rozanolixizumab was supported by UCB; Dr. Robak reported disclosures related to UCB (honoraria, research funding), as well as Takeda, Janssen, Amgen, Roche, AbbVie, Gilead, BeiGene, Acerta, and MorphoSys. The study of efgartigimod was supported by argenx; Dr. Newland reported disclosures related to argenx, Novartis, Angle, Amgen, Ono Pharmaceutical, Shionogi, Rigel, and Dova Pharmaceuticals.
SOURCEs: Robak T et al. ASH 2019, Abstract 897; Newland AC et al. ASH 2019, Abstract 895.
ORLANDO – Treatments targeted to the neonatal Fc receptor are showing promise in phase 2 studies in primary immune thrombocytopenia, investigators reported at the annual meeting of the American Society of Hematology.
Encouraging outcomes support the continued phase 3 development of these agents, which are designed to block the neonatal Fc receptor (FcRn) in patients with this IgG-mediated disease.
Blocking FcRN is intended to prevent recycling of IgG, resulting in IgG degradation, according to the authors of studies evaluating rozanolixizumab, a subcutaneously administered monoclonal antibody, and efgartigimod, an intravenously administered antibody fragment, in primary immune thrombocytopenia (ITP).
Rozanolixizumab
Results of the phase 2 study of rozanolixizumab demonstrated that this agent reduced IgG levels and improved platelet counts at all doses tested, according to the investigators, led by Tadeusz Robak, MD, of the department of hematology at the Medical University of Lodz (Poland).
Efficacy endpoints were seen more quickly – by day 8 of treatment – with single subcutaneous infusions at higher doses, according to the researchers.
Headaches of mild to moderate severity were noted at higher doses, and no patients left the study because of adverse events, they reported.
“These safety, tolerability, and efficacy data support phase 3 development of rozanolixizumab in patients with primary ITP,” wrote Dr. Robak and coauthors in the abstract for their study.
A total of 66 adult patients with primary ITP were enrolled and treated with single or multiple subcutaneous doses of rozanolixizumab administered at 1-week intervals.
Baseline characteristics suggested a “difficult-to-treat” patient cohort that had a median ITP duration of nearly 6 years and a median of four prior therapies, including thrombopoietin receptor agonists in about one-third of patients, according to the investigators.
Platelet counts of at least 50 x 109/L were achieved by day 8 in more than half of patients who received single doses of rozanolixizumab at higher dose levels of 15 mg/kg (58.3%) and 20 mg/kg (54.5%), Dr. Robak and colleagues reported.
Mild to moderate headaches were seen in about 40% of patients over an 8-week observation period. There were no serious infections and, of four serious adverse events occurring during the study, none were deemed to be treatment related, according to the investigators.
“People who have primary ITP may experience low platelet count that can put them at risk for severe bleeding, and there are limited options that provide a rapid increase in platelet count to reduce this risk,” Dr. Robak said in an interview. “These data build on the growing body of evidence that suggest targeting the FcRn pathway could have the potential to transform the treatment experience for people with rare IgG autoantibody–mediated diseases such as primary ITP.”
Efgartigimod
Substantial reductions in IgG levels and clinically relevant increases in platelet counts were seen following a 3-week treatment cycle with efgartigimod in patients with treatment-refractory ITP, according to investigator Adrian C. Newland, MB, BCh, of the Royal London Hospital and coinvestigators.
The human IgG1 antibody Fc-fragment, a natural ligand of FcRN, is engineered to have increased affinity to FcRn, while preserving its pH‐dependent binding, according to the investigators.
Efgartigimod treatment was well tolerated and reduced the proportion of patients with bleeding in the phase 2 study presented at ASH 2019.
“This suggests that targeted IgG reduction with efgartigimod is a potential new treatment modality in primary ITP, and warrants evaluation of longer-term treatment in a larger phase 3 study,” the investigators reported in the abstract for their study.
The report described 38 patients randomized to four weekly intravenous infusions of placebo or efgartigimod at one of two dosing levels. Patients had long-standing ITP, with a median 4.8 years disease duration, and all had either failed splenectomy or had inadequate response to prior treatment.
Efgartigimod treatment rapidly reduced total IgG in all patients who received it, with a mean change from baseline of up to 63.7%, according to investigators.
Platelet counts favored the investigational treatment over placebo by several measures. Platelet counts of at least 50 x 109/L on two or more occasions were seen in 46% of efgartigimod-treated patients and 25% of the placebo group; that platelet count was achieved for 10 or more days in 38% and 0% of the efgartigimod and placebo groups, respectively.
Treatment was well tolerated, according to the investigators, who said there were “no dose-related safety observations.” Full results of the phase 2 investigation were published in the American Journal of Hematology, concurrent with the meeting (2019 Dec 10. doi.org/10.1002/ajh.25680).
The study of rozanolixizumab was supported by UCB; Dr. Robak reported disclosures related to UCB (honoraria, research funding), as well as Takeda, Janssen, Amgen, Roche, AbbVie, Gilead, BeiGene, Acerta, and MorphoSys. The study of efgartigimod was supported by argenx; Dr. Newland reported disclosures related to argenx, Novartis, Angle, Amgen, Ono Pharmaceutical, Shionogi, Rigel, and Dova Pharmaceuticals.
SOURCEs: Robak T et al. ASH 2019, Abstract 897; Newland AC et al. ASH 2019, Abstract 895.
REPORTING FROM ASH 2019
Poor sleep due to ADHD or ADHD due to poor sleep?
The day wouldn’t be so bad if he would just go to sleep at night! How many times have you heard this plea from parents of your patients with ADHD? Sleep is important for everyone, but getting enough is both more important and more difficult for children with ADHD. About three-quarters of children with ADHD have significant problems with sleep, most even before any medication treatment. And inadequate sleep can exacerbate or even cause ADHD symptoms!
Solving sleep problems for children with ADHD is not always simple. The kinds of sleep issues that are more common in children (and adults) with ADHD, compared with typical children, include behavioral bedtime resistance, circadian rhythm sleep disorder (CRSD), insomnia, morning sleepiness, night waking, periodic limb movement disorder (PLMD), restless leg syndrome (RLS), and sleep disordered breathing (SDB). Such a broad differential means a careful history and sometimes even lab studies may be needed.
Both initial and follow-up visits for ADHD should include a sleep history or, ideally, a tool such as BEARS sleep screening tool or Children’s Sleep Habits Questionnaire and a 2-week sleep diary (http://www.sleepfoundation.org/). These are good ways to collect signs of allergies or apnea (for SDB), limb movements or limb pain (for RLS or PLMD), mouth breathing, night waking, and snoring.
You also need to ask about alcohol, drugs, caffeine, and nicotine; asthma; comorbid conditions such as mental health disorders or their treatments; and enuresis (alone or part of nocturnal seizures).
Do I need to remind you to find out about electronics activating the child before bedtime – hidden under the covers, or signaling messages from friends in the middle of the night – and to encourage limits on these? Some sleep disorders warrant polysomnography in a sleep lab or from MyZeo.com (for PLMD and some SDB) or ferritin less than 50 mg/L (for RLS) for diagnosis and to guide treatment. Nasal steroids, antihistamines, or montelukast may help SDB when there are enlarged tonsils or adenoids, but adenotonsillectomy is usually curative.
The first line and most effective treatment for sleep problems in children with or without ADHD is improving sleep hygiene. The key component is establishing habits for the entire sleep cycle: a steady pattern of reduced stimulation in the hour before bedtime (sans electronics); a friendly rather than irritated bedtime routine; and the same bedtime and wake up time, ideally 7 days per week. Bedtime stories read to the child can soothe at any age, not just toddlers! Of course, both children and families want fun and special occasions. For most, varying bedtime by up to 1 hour won’t mess up their biological clock, but for some even this should be avoided. Sleeping alone in a cool, dark, quiet room, nightly in the same bed (not used for other activities), is considered the ideal. Earplugs, white noise generators, and eye masks may be helpful. If sleeping with siblings is a necessity, bedtimes can be staggered to put the child to bed earlier or after others are asleep.
Struggles postponing bedtime may be part of a pattern of oppositionality common in ADHD, but the child may not be tired due to being off schedule (from CRSD), napping on the bus or after school, sleeping in mornings, or unrealistic parent expectations for sleep duration. Parents may want their hyperactive children to give them a break and go to bed at 8 p.m., but children aged 6-10 years need only 10-11 hours and those aged 10-17 years need 8.5-9.25 hours of sleep.
Not tired may instead be “wired” from lingering stimulant effects or even lack of such medication leaving the child overactive or rebounding from earlier medications. Lower afternoon doses or shorter-acting medication may solve lasting medication issues, but sometimes an additional low dose of stimulants actually will help a child with ADHD settle at bedtime. All stimulant medications can prolong sleep onset, often by 30 minutes, but this varies by individual and tends to resolve on its own a few weeks after a new or changed medicine. Switching medication category may allow a child to fall asleep faster. Atomoxetine and alpha agonists are less likely to delay sleep than methylphenidate (MPH).
What if sleep hygiene, behavioral methods, and adjusting ADHD medications is not enough? If sleep issues are causing significant problems, medication for sleep is worth a try. Controlled-release melatonin 1-2 hours before bedtime has data for effectiveness. There is no defined dose, so the lowest effective dose should be used, but 3-6 mg may be needed. Because many families with a child with ADHD are not organized enough to give medicine on this schedule, sublingual melatonin that acts in 15-20 minutes is a good alternative or even first choice. Clonidine 0.05-0.2 mg 1 hour before bedtime speeds sleep onset, lasts 3 hours, and does not carry over to sedation the next day. Stronger psychopharmaceuticals can assist sleep onset, including low dose mirtazapine or trazodone, but have the side effect of daytime sleepiness.
Management of waking in the middle of the night can be more difficult to treat as sleep drive has been dissipated. First, consider whether trips out of bed reflect a sleep association that has not been extinguished. Daytime atomoxetine or, better yet, MPH may improve night waking, and sometimes even a low-dose evening, long-acting medication, such as osmotic release oral system (OROS) extended release methylphenidate HCL (OROS MPH), helps. Short-acting clonidine or melatonin in the middle of the night or bedtime mirtazapine or trazodone also may be worth a try.
When dealing with sleep, keep in mind that 50% or more of children with ADHD have a coexisting mental health disorder. Anxiety, separation anxiety, depression, and dysthymia all often affect sleep onset, night waking, and sometimes early morning waking. The child or teen may need extra reassurance or company at bedtime (siblings or pets may suffice). Reading positive stories or playing soft music may be better at setting a positive mood and sense of safety for sleep, certainly more so than social media, which should be avoided.
Keep in mind that substance use is more common in ADHD as well as with those other mental health conditions and can interfere with restful sleep and make RLS worse. Bipolar disorder can be mistaken for ADHD as it often presents with hyperactivity but also can be comorbid. Sleep problems are increased sixfold when both are present. Prolonged periods awake at night and diminished need for sleep are signs that help differentiate bipolar from ADHD. Medication management for the bipolar disorder with atypicals can reduce sleep latency and reduce REM sleep, but also causes morning fatigue. Medications to treat other mental health problems can help sleep onset (for example, anticonvulsants, atypicals), or prolong it (SSRIs), change REM states (atypicals), and even exacerbate RLS (SSRIs). You can make changes or work with the child’s mental health specialist if medications are causing significant sleep problems.
When we help improve sleep for children with ADHD, it can lessen not only ADHD symptoms but also some symptoms of other mental health disorders, improve learning and behavior, and greatly improve family quality of life!
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].
The day wouldn’t be so bad if he would just go to sleep at night! How many times have you heard this plea from parents of your patients with ADHD? Sleep is important for everyone, but getting enough is both more important and more difficult for children with ADHD. About three-quarters of children with ADHD have significant problems with sleep, most even before any medication treatment. And inadequate sleep can exacerbate or even cause ADHD symptoms!
Solving sleep problems for children with ADHD is not always simple. The kinds of sleep issues that are more common in children (and adults) with ADHD, compared with typical children, include behavioral bedtime resistance, circadian rhythm sleep disorder (CRSD), insomnia, morning sleepiness, night waking, periodic limb movement disorder (PLMD), restless leg syndrome (RLS), and sleep disordered breathing (SDB). Such a broad differential means a careful history and sometimes even lab studies may be needed.
Both initial and follow-up visits for ADHD should include a sleep history or, ideally, a tool such as BEARS sleep screening tool or Children’s Sleep Habits Questionnaire and a 2-week sleep diary (http://www.sleepfoundation.org/). These are good ways to collect signs of allergies or apnea (for SDB), limb movements or limb pain (for RLS or PLMD), mouth breathing, night waking, and snoring.
You also need to ask about alcohol, drugs, caffeine, and nicotine; asthma; comorbid conditions such as mental health disorders or their treatments; and enuresis (alone or part of nocturnal seizures).
Do I need to remind you to find out about electronics activating the child before bedtime – hidden under the covers, or signaling messages from friends in the middle of the night – and to encourage limits on these? Some sleep disorders warrant polysomnography in a sleep lab or from MyZeo.com (for PLMD and some SDB) or ferritin less than 50 mg/L (for RLS) for diagnosis and to guide treatment. Nasal steroids, antihistamines, or montelukast may help SDB when there are enlarged tonsils or adenoids, but adenotonsillectomy is usually curative.
The first line and most effective treatment for sleep problems in children with or without ADHD is improving sleep hygiene. The key component is establishing habits for the entire sleep cycle: a steady pattern of reduced stimulation in the hour before bedtime (sans electronics); a friendly rather than irritated bedtime routine; and the same bedtime and wake up time, ideally 7 days per week. Bedtime stories read to the child can soothe at any age, not just toddlers! Of course, both children and families want fun and special occasions. For most, varying bedtime by up to 1 hour won’t mess up their biological clock, but for some even this should be avoided. Sleeping alone in a cool, dark, quiet room, nightly in the same bed (not used for other activities), is considered the ideal. Earplugs, white noise generators, and eye masks may be helpful. If sleeping with siblings is a necessity, bedtimes can be staggered to put the child to bed earlier or after others are asleep.
Struggles postponing bedtime may be part of a pattern of oppositionality common in ADHD, but the child may not be tired due to being off schedule (from CRSD), napping on the bus or after school, sleeping in mornings, or unrealistic parent expectations for sleep duration. Parents may want their hyperactive children to give them a break and go to bed at 8 p.m., but children aged 6-10 years need only 10-11 hours and those aged 10-17 years need 8.5-9.25 hours of sleep.
Not tired may instead be “wired” from lingering stimulant effects or even lack of such medication leaving the child overactive or rebounding from earlier medications. Lower afternoon doses or shorter-acting medication may solve lasting medication issues, but sometimes an additional low dose of stimulants actually will help a child with ADHD settle at bedtime. All stimulant medications can prolong sleep onset, often by 30 minutes, but this varies by individual and tends to resolve on its own a few weeks after a new or changed medicine. Switching medication category may allow a child to fall asleep faster. Atomoxetine and alpha agonists are less likely to delay sleep than methylphenidate (MPH).
What if sleep hygiene, behavioral methods, and adjusting ADHD medications is not enough? If sleep issues are causing significant problems, medication for sleep is worth a try. Controlled-release melatonin 1-2 hours before bedtime has data for effectiveness. There is no defined dose, so the lowest effective dose should be used, but 3-6 mg may be needed. Because many families with a child with ADHD are not organized enough to give medicine on this schedule, sublingual melatonin that acts in 15-20 minutes is a good alternative or even first choice. Clonidine 0.05-0.2 mg 1 hour before bedtime speeds sleep onset, lasts 3 hours, and does not carry over to sedation the next day. Stronger psychopharmaceuticals can assist sleep onset, including low dose mirtazapine or trazodone, but have the side effect of daytime sleepiness.
Management of waking in the middle of the night can be more difficult to treat as sleep drive has been dissipated. First, consider whether trips out of bed reflect a sleep association that has not been extinguished. Daytime atomoxetine or, better yet, MPH may improve night waking, and sometimes even a low-dose evening, long-acting medication, such as osmotic release oral system (OROS) extended release methylphenidate HCL (OROS MPH), helps. Short-acting clonidine or melatonin in the middle of the night or bedtime mirtazapine or trazodone also may be worth a try.
When dealing with sleep, keep in mind that 50% or more of children with ADHD have a coexisting mental health disorder. Anxiety, separation anxiety, depression, and dysthymia all often affect sleep onset, night waking, and sometimes early morning waking. The child or teen may need extra reassurance or company at bedtime (siblings or pets may suffice). Reading positive stories or playing soft music may be better at setting a positive mood and sense of safety for sleep, certainly more so than social media, which should be avoided.
Keep in mind that substance use is more common in ADHD as well as with those other mental health conditions and can interfere with restful sleep and make RLS worse. Bipolar disorder can be mistaken for ADHD as it often presents with hyperactivity but also can be comorbid. Sleep problems are increased sixfold when both are present. Prolonged periods awake at night and diminished need for sleep are signs that help differentiate bipolar from ADHD. Medication management for the bipolar disorder with atypicals can reduce sleep latency and reduce REM sleep, but also causes morning fatigue. Medications to treat other mental health problems can help sleep onset (for example, anticonvulsants, atypicals), or prolong it (SSRIs), change REM states (atypicals), and even exacerbate RLS (SSRIs). You can make changes or work with the child’s mental health specialist if medications are causing significant sleep problems.
When we help improve sleep for children with ADHD, it can lessen not only ADHD symptoms but also some symptoms of other mental health disorders, improve learning and behavior, and greatly improve family quality of life!
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].
The day wouldn’t be so bad if he would just go to sleep at night! How many times have you heard this plea from parents of your patients with ADHD? Sleep is important for everyone, but getting enough is both more important and more difficult for children with ADHD. About three-quarters of children with ADHD have significant problems with sleep, most even before any medication treatment. And inadequate sleep can exacerbate or even cause ADHD symptoms!
Solving sleep problems for children with ADHD is not always simple. The kinds of sleep issues that are more common in children (and adults) with ADHD, compared with typical children, include behavioral bedtime resistance, circadian rhythm sleep disorder (CRSD), insomnia, morning sleepiness, night waking, periodic limb movement disorder (PLMD), restless leg syndrome (RLS), and sleep disordered breathing (SDB). Such a broad differential means a careful history and sometimes even lab studies may be needed.
Both initial and follow-up visits for ADHD should include a sleep history or, ideally, a tool such as BEARS sleep screening tool or Children’s Sleep Habits Questionnaire and a 2-week sleep diary (http://www.sleepfoundation.org/). These are good ways to collect signs of allergies or apnea (for SDB), limb movements or limb pain (for RLS or PLMD), mouth breathing, night waking, and snoring.
You also need to ask about alcohol, drugs, caffeine, and nicotine; asthma; comorbid conditions such as mental health disorders or their treatments; and enuresis (alone or part of nocturnal seizures).
Do I need to remind you to find out about electronics activating the child before bedtime – hidden under the covers, or signaling messages from friends in the middle of the night – and to encourage limits on these? Some sleep disorders warrant polysomnography in a sleep lab or from MyZeo.com (for PLMD and some SDB) or ferritin less than 50 mg/L (for RLS) for diagnosis and to guide treatment. Nasal steroids, antihistamines, or montelukast may help SDB when there are enlarged tonsils or adenoids, but adenotonsillectomy is usually curative.
The first line and most effective treatment for sleep problems in children with or without ADHD is improving sleep hygiene. The key component is establishing habits for the entire sleep cycle: a steady pattern of reduced stimulation in the hour before bedtime (sans electronics); a friendly rather than irritated bedtime routine; and the same bedtime and wake up time, ideally 7 days per week. Bedtime stories read to the child can soothe at any age, not just toddlers! Of course, both children and families want fun and special occasions. For most, varying bedtime by up to 1 hour won’t mess up their biological clock, but for some even this should be avoided. Sleeping alone in a cool, dark, quiet room, nightly in the same bed (not used for other activities), is considered the ideal. Earplugs, white noise generators, and eye masks may be helpful. If sleeping with siblings is a necessity, bedtimes can be staggered to put the child to bed earlier or after others are asleep.
Struggles postponing bedtime may be part of a pattern of oppositionality common in ADHD, but the child may not be tired due to being off schedule (from CRSD), napping on the bus or after school, sleeping in mornings, or unrealistic parent expectations for sleep duration. Parents may want their hyperactive children to give them a break and go to bed at 8 p.m., but children aged 6-10 years need only 10-11 hours and those aged 10-17 years need 8.5-9.25 hours of sleep.
Not tired may instead be “wired” from lingering stimulant effects or even lack of such medication leaving the child overactive or rebounding from earlier medications. Lower afternoon doses or shorter-acting medication may solve lasting medication issues, but sometimes an additional low dose of stimulants actually will help a child with ADHD settle at bedtime. All stimulant medications can prolong sleep onset, often by 30 minutes, but this varies by individual and tends to resolve on its own a few weeks after a new or changed medicine. Switching medication category may allow a child to fall asleep faster. Atomoxetine and alpha agonists are less likely to delay sleep than methylphenidate (MPH).
What if sleep hygiene, behavioral methods, and adjusting ADHD medications is not enough? If sleep issues are causing significant problems, medication for sleep is worth a try. Controlled-release melatonin 1-2 hours before bedtime has data for effectiveness. There is no defined dose, so the lowest effective dose should be used, but 3-6 mg may be needed. Because many families with a child with ADHD are not organized enough to give medicine on this schedule, sublingual melatonin that acts in 15-20 minutes is a good alternative or even first choice. Clonidine 0.05-0.2 mg 1 hour before bedtime speeds sleep onset, lasts 3 hours, and does not carry over to sedation the next day. Stronger psychopharmaceuticals can assist sleep onset, including low dose mirtazapine or trazodone, but have the side effect of daytime sleepiness.
Management of waking in the middle of the night can be more difficult to treat as sleep drive has been dissipated. First, consider whether trips out of bed reflect a sleep association that has not been extinguished. Daytime atomoxetine or, better yet, MPH may improve night waking, and sometimes even a low-dose evening, long-acting medication, such as osmotic release oral system (OROS) extended release methylphenidate HCL (OROS MPH), helps. Short-acting clonidine or melatonin in the middle of the night or bedtime mirtazapine or trazodone also may be worth a try.
When dealing with sleep, keep in mind that 50% or more of children with ADHD have a coexisting mental health disorder. Anxiety, separation anxiety, depression, and dysthymia all often affect sleep onset, night waking, and sometimes early morning waking. The child or teen may need extra reassurance or company at bedtime (siblings or pets may suffice). Reading positive stories or playing soft music may be better at setting a positive mood and sense of safety for sleep, certainly more so than social media, which should be avoided.
Keep in mind that substance use is more common in ADHD as well as with those other mental health conditions and can interfere with restful sleep and make RLS worse. Bipolar disorder can be mistaken for ADHD as it often presents with hyperactivity but also can be comorbid. Sleep problems are increased sixfold when both are present. Prolonged periods awake at night and diminished need for sleep are signs that help differentiate bipolar from ADHD. Medication management for the bipolar disorder with atypicals can reduce sleep latency and reduce REM sleep, but also causes morning fatigue. Medications to treat other mental health problems can help sleep onset (for example, anticonvulsants, atypicals), or prolong it (SSRIs), change REM states (atypicals), and even exacerbate RLS (SSRIs). You can make changes or work with the child’s mental health specialist if medications are causing significant sleep problems.
When we help improve sleep for children with ADHD, it can lessen not only ADHD symptoms but also some symptoms of other mental health disorders, improve learning and behavior, and greatly improve family quality of life!
Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].