ORLANDO – Among children with genetic risks for type 1 diabetes and autoantibodies against pancreatic islet cells, a hemoglobin A_1c at or above 5.6% strongly predicts the onset of type 1 diabetes within a year, according to investigators from The Environmental Determinants of Diabetes in the Young (TEDDY) study.

M. Alexander Otto/MDedge News

The risk is even greater if other factors – age at A_1c test, month of A_1c test, continent of residence, and the z-score for one antibody in particular, IA2A, a tyrosine phosphatase antigen protein – are taken into account, with an area under the curve (AUC) of about 0.97. The study team is developing an online risk calculator for clinicians so they can simply plug in the numbers.

But the 5.6% cutpoint works well even by itself, with an AUC of about 0.86. Among the children with genetic risk factors and islet cell autoantibodies who hit that mark in the study, the median time to diagnosis of type 1 diabetes mellitus (T1DM) was 7.1 months.

The point of the work is to catch disease onset early to prevent children from going into diabetic ketoacidosis.

The ultimate goal of TEDDY is to identify infectious agents, dietary factors, and other environmental agents that either trigger or protect against T1DM in genetically susceptible children, to develop strategies to prevent, delay, or even reverse T1DM. For more than a decade, the consortium has been following more than 8,000 children who screened positive at birth for genetic anomalies in the human leukocyte antigen region on their 6th chromosome, a major risk factor for T1DM. The team is following them to find out what puts them over the edge; A_1c seems to be key.

Catching the disease early is a goal. Until now, the TEDDY team has used the development of pancreatic islet cell autoantibodies to trigger oral glucose tolerance tests (OGTTs) every 6 months.

The problem is that islet antibodies “are great at saying that you are going to get diabetes but not when. We have kids who have been multiple antibody positive now for 6, 7, 8 years” but who still haven’t developed T1DM. In the meantime, their parents have been dragging them in for OGTTs every 6 months for years, said lead investigator and TEDDY study coordinator Michael Killian, of the Pacific Northwest Research Institute, Seattle.

With the A_1c cutpoint, it should be safe to hold off on direct glycemic surveillance until A_1c levels reach 5.6%, and even safer when the full risk prediction model with 1A2A z-scores and other factors are available. Once children hit the parameters, it’s near certain they will develop T1DM within a year, so the findings should reduce the number of OGTT tests to just two or three. In the end, “we’ll get better compliance” with testing and still “catch these kids early,” Mr. Killian said at the annual scientific sessions of the American Diabetes Association.

Rare is the newborn who is screened for diabetes risk at birth, and even rarer is the child who is followed for autoantibodies. If the findings hold out, however, such early action could be the future.

“We envision a time” when newborns are screened for T1DM risk and followed for autoantibodies. Glycemic surveillance will kick in if they hit A_1c levels of 5.6%, said William Hagopian, MD, PhD, clinical associate professor at the University of Washington, Seattle, and a TEDDY principal investigator.

Among the 8,000-plus children followed, 456 had persistent islet autoantibodies and at least three A_1c tests in the prior 12 months; 104 progressed to T1DM and 352 did not. The mean age to islet autoantibody seroconversion was 43 months, and mean age to T1DM diagnosis was 73 months. The team ran a receiver operating curve analysis to identify the optimum A_1c cutpoint, 5.6%.

The month of testing mattered, because “glycemia is higher in the winter, lower in the summer, and insulin sensitivity is lower in the winter, and higher in the summer,” Dr. Hagopian said. It probably has something to do with what the stresses of early human evolution bred into the genes.

The IA2A autoantibody z-score is the only number that will be cumbersome to plug into the upcoming online risk calculator. It’s the number of standard deviations off your reference lab’s mean. “You have to talk to the lab that does your IA2As to know what the standard deviation is,” Dr. Hagopian said.

The investigators had no disclosures. TEDDY is supported by the National Institutes of Health, among other entities.

[email protected]

SOURCE: Killian M et al. ADA 2018, Abstract 162-LB

ORLANDO – Among children with genetic risks for type 1 diabetes and autoantibodies against pancreatic islet cells, a hemoglobin A_1c at or above 5.6% strongly predicts the onset of type 1 diabetes within a year, according to investigators from The Environmental Determinants of Diabetes in the Young (TEDDY) study.

M. Alexander Otto/MDedge News

The risk is even greater if other factors – age at A_1c test, month of A_1c test, continent of residence, and the z-score for one antibody in particular, IA2A, a tyrosine phosphatase antigen protein – are taken into account, with an area under the curve (AUC) of about 0.97. The study team is developing an online risk calculator for clinicians so they can simply plug in the numbers.

But the 5.6% cutpoint works well even by itself, with an AUC of about 0.86. Among the children with genetic risk factors and islet cell autoantibodies who hit that mark in the study, the median time to diagnosis of type 1 diabetes mellitus (T1DM) was 7.1 months.

The point of the work is to catch disease onset early to prevent children from going into diabetic ketoacidosis.

The ultimate goal of TEDDY is to identify infectious agents, dietary factors, and other environmental agents that either trigger or protect against T1DM in genetically susceptible children, to develop strategies to prevent, delay, or even reverse T1DM. For more than a decade, the consortium has been following more than 8,000 children who screened positive at birth for genetic anomalies in the human leukocyte antigen region on their 6th chromosome, a major risk factor for T1DM. The team is following them to find out what puts them over the edge; A_1c seems to be key.

Catching the disease early is a goal. Until now, the TEDDY team has used the development of pancreatic islet cell autoantibodies to trigger oral glucose tolerance tests (OGTTs) every 6 months.

The problem is that islet antibodies “are great at saying that you are going to get diabetes but not when. We have kids who have been multiple antibody positive now for 6, 7, 8 years” but who still haven’t developed T1DM. In the meantime, their parents have been dragging them in for OGTTs every 6 months for years, said lead investigator and TEDDY study coordinator Michael Killian, of the Pacific Northwest Research Institute, Seattle.

With the A_1c cutpoint, it should be safe to hold off on direct glycemic surveillance until A_1c levels reach 5.6%, and even safer when the full risk prediction model with 1A2A z-scores and other factors are available. Once children hit the parameters, it’s near certain they will develop T1DM within a year, so the findings should reduce the number of OGTT tests to just two or three. In the end, “we’ll get better compliance” with testing and still “catch these kids early,” Mr. Killian said at the annual scientific sessions of the American Diabetes Association.

Rare is the newborn who is screened for diabetes risk at birth, and even rarer is the child who is followed for autoantibodies. If the findings hold out, however, such early action could be the future.

“We envision a time” when newborns are screened for T1DM risk and followed for autoantibodies. Glycemic surveillance will kick in if they hit A_1c levels of 5.6%, said William Hagopian, MD, PhD, clinical associate professor at the University of Washington, Seattle, and a TEDDY principal investigator.

Among the 8,000-plus children followed, 456 had persistent islet autoantibodies and at least three A_1c tests in the prior 12 months; 104 progressed to T1DM and 352 did not. The mean age to islet autoantibody seroconversion was 43 months, and mean age to T1DM diagnosis was 73 months. The team ran a receiver operating curve analysis to identify the optimum A_1c cutpoint, 5.6%.

The month of testing mattered, because “glycemia is higher in the winter, lower in the summer, and insulin sensitivity is lower in the winter, and higher in the summer,” Dr. Hagopian said. It probably has something to do with what the stresses of early human evolution bred into the genes.

The IA2A autoantibody z-score is the only number that will be cumbersome to plug into the upcoming online risk calculator. It’s the number of standard deviations off your reference lab’s mean. “You have to talk to the lab that does your IA2As to know what the standard deviation is,” Dr. Hagopian said.

The investigators had no disclosures. TEDDY is supported by the National Institutes of Health, among other entities.

[email protected]

SOURCE: Killian M et al. ADA 2018, Abstract 162-LB

ORLANDO – Among children with genetic risks for type 1 diabetes and autoantibodies against pancreatic islet cells, a hemoglobin A_1c at or above 5.6% strongly predicts the onset of type 1 diabetes within a year, according to investigators from The Environmental Determinants of Diabetes in the Young (TEDDY) study.

M. Alexander Otto/MDedge News

The risk is even greater if other factors – age at A_1c test, month of A_1c test, continent of residence, and the z-score for one antibody in particular, IA2A, a tyrosine phosphatase antigen protein – are taken into account, with an area under the curve (AUC) of about 0.97. The study team is developing an online risk calculator for clinicians so they can simply plug in the numbers.

But the 5.6% cutpoint works well even by itself, with an AUC of about 0.86. Among the children with genetic risk factors and islet cell autoantibodies who hit that mark in the study, the median time to diagnosis of type 1 diabetes mellitus (T1DM) was 7.1 months.

The point of the work is to catch disease onset early to prevent children from going into diabetic ketoacidosis.

The ultimate goal of TEDDY is to identify infectious agents, dietary factors, and other environmental agents that either trigger or protect against T1DM in genetically susceptible children, to develop strategies to prevent, delay, or even reverse T1DM. For more than a decade, the consortium has been following more than 8,000 children who screened positive at birth for genetic anomalies in the human leukocyte antigen region on their 6th chromosome, a major risk factor for T1DM. The team is following them to find out what puts them over the edge; A_1c seems to be key.

Catching the disease early is a goal. Until now, the TEDDY team has used the development of pancreatic islet cell autoantibodies to trigger oral glucose tolerance tests (OGTTs) every 6 months.

The problem is that islet antibodies “are great at saying that you are going to get diabetes but not when. We have kids who have been multiple antibody positive now for 6, 7, 8 years” but who still haven’t developed T1DM. In the meantime, their parents have been dragging them in for OGTTs every 6 months for years, said lead investigator and TEDDY study coordinator Michael Killian, of the Pacific Northwest Research Institute, Seattle.

With the A_1c cutpoint, it should be safe to hold off on direct glycemic surveillance until A_1c levels reach 5.6%, and even safer when the full risk prediction model with 1A2A z-scores and other factors are available. Once children hit the parameters, it’s near certain they will develop T1DM within a year, so the findings should reduce the number of OGTT tests to just two or three. In the end, “we’ll get better compliance” with testing and still “catch these kids early,” Mr. Killian said at the annual scientific sessions of the American Diabetes Association.

Rare is the newborn who is screened for diabetes risk at birth, and even rarer is the child who is followed for autoantibodies. If the findings hold out, however, such early action could be the future.

“We envision a time” when newborns are screened for T1DM risk and followed for autoantibodies. Glycemic surveillance will kick in if they hit A_1c levels of 5.6%, said William Hagopian, MD, PhD, clinical associate professor at the University of Washington, Seattle, and a TEDDY principal investigator.

Among the 8,000-plus children followed, 456 had persistent islet autoantibodies and at least three A_1c tests in the prior 12 months; 104 progressed to T1DM and 352 did not. The mean age to islet autoantibody seroconversion was 43 months, and mean age to T1DM diagnosis was 73 months. The team ran a receiver operating curve analysis to identify the optimum A_1c cutpoint, 5.6%.

The month of testing mattered, because “glycemia is higher in the winter, lower in the summer, and insulin sensitivity is lower in the winter, and higher in the summer,” Dr. Hagopian said. It probably has something to do with what the stresses of early human evolution bred into the genes.

The IA2A autoantibody z-score is the only number that will be cumbersome to plug into the upcoming online risk calculator. It’s the number of standard deviations off your reference lab’s mean. “You have to talk to the lab that does your IA2As to know what the standard deviation is,” Dr. Hagopian said.

The investigators had no disclosures. TEDDY is supported by the National Institutes of Health, among other entities.

[email protected]

SOURCE: Killian M et al. ADA 2018, Abstract 162-LB

AMSTERDAM – Middle-aged and elderly people infected with HIV were more likely to meet an established definition of frailty than were uninfected people of the same age, and during 4 years of follow-up frailty significantly linked with an increased incidence of both mortality and development of new comorbidities, based on a Dutch prospective study of 1,146 people.

Mitchel L. Zoler/MDedge News

People living with HIV also showed, despite antiretroviral treatment, a significantly increased rate of progression to frailty over the course of 4 years, compared with uninfected people, after adjustment for demographic differences. This progression to frailty appeared mediated by a high waist-to-hip ratio, a higher number of preexisting comorbidities, and symptoms of depression, Eveline Verheij, MD, said at the 22nd International AIDS Conference.

At entry into the study, people living with HIV had a 10% prevalence of frailty, compared with 3% among those who were uninfected, said Dr. Verheij, a researcher with the Amsterdam Institute for Global Health & Development. She defined frailty using criteria first introduced by researchers in 2001, which established five characteristics as markers of frailty: slow gait, low grip strength, a low level of physical activity, self-reported exhaustion, and unintentional weight loss of at least 10 pounds during the preceding year (J Gerontol A Biol Sci Med. 2001 Mar 1;56[3]:M146-57).

People with three or more of these conditions were identified as frail, those with one or two were tagged as prefrail, and people with none of these five characteristics were considered robust.

In the study reported by Dr. Verheij, the prevalence of people identified as robust at the time they entered the study was about 60% of those without an HIV infection and about 40% of those infected with HIV. During the 4 years she and her associates followed these people, their rates of progression from a robust state to frailty occurred more than twice as often among the people living with HIV, compared with those who were uninfected, after adjustment for age, ethnicity, and education.

Dr. Verheij admitted that she and her associates have not identified interventions that are effective for reversing frailty. “People who are already frail are likely to remain frail,” she noted. A better strategy is to take steps to defer frailty and help people who are robust retain that status. This could involve measures such as smoking cessation, exercise, and maintaining or expanding social networks, she suggested.

The AGEhiV Cohort Study enrolled 596 people living with HIV and 550 uninfected people who were all at least 45 years old. The average age was 52 years, with about 10% in each group older than 65 years. About 90% of the enrollees were Dutch, nearly three-quarters of those in both groups were men who have sex with men, and 14% of those who were uninfected and 20% of those living with HIV had symptoms of depression.

At baseline, 61% of those without HIV and 48% of people with HIV had no comorbidities, and while the percentage in both groups with one comorbidity at entry was nearly the same, 28% and 31%, respectively, the percentage with two or more comorbidities was more divergent. Among those without HIV infection, 8% had two comorbidities and 3% had three or more, while among those with HIV, 14% had two comorbidities and 6% had three or more.

The people living with HIV had been infected for an average of 12 years. At enrollment, 96% were on antiretroviral therapy, and those on treatment had received it for an average of 10 years. At enrollment, their average CD4 cell count was 565 cells/mm³. Their average nadir cell count had been 170 cells/mm³, and 32% had a history of being diagnosed with AIDS.

Dr. Verheij and her associates examined each participant at baseline and twice more, 2 and 4 years after enrollment. During the 4 years of follow-up, 17 people died. After adjustment for age, baseline comorbidities, and HIV infection, the mortality was more than 10-fold higher among people who had been frail at entry, compared with those who were robust.

During follow-up, 276 of all enrollees developed 329 comorbidities. The four most common incident comorbidities were hypertension, followed by chronic obstructive lung disease, renal insufficiency, and osteoporosis. These four conditions accounted for three-quarters of all incident comorbidities. After adjustment for demographics, baseline comorbidities, and HIV status, people who entered the study as frail or who became frail during the study had about a 90% increased rate of developing a new comorbidity compared with those who were not frail.

[email protected]

SOURCE: Verheij E et al. AIDS 2018, Abstract 9303, THAB01015.

AMSTERDAM – Middle-aged and elderly people infected with HIV were more likely to meet an established definition of frailty than were uninfected people of the same age, and during 4 years of follow-up frailty significantly linked with an increased incidence of both mortality and development of new comorbidities, based on a Dutch prospective study of 1,146 people.

Mitchel L. Zoler/MDedge News

People living with HIV also showed, despite antiretroviral treatment, a significantly increased rate of progression to frailty over the course of 4 years, compared with uninfected people, after adjustment for demographic differences. This progression to frailty appeared mediated by a high waist-to-hip ratio, a higher number of preexisting comorbidities, and symptoms of depression, Eveline Verheij, MD, said at the 22nd International AIDS Conference.

At entry into the study, people living with HIV had a 10% prevalence of frailty, compared with 3% among those who were uninfected, said Dr. Verheij, a researcher with the Amsterdam Institute for Global Health & Development. She defined frailty using criteria first introduced by researchers in 2001, which established five characteristics as markers of frailty: slow gait, low grip strength, a low level of physical activity, self-reported exhaustion, and unintentional weight loss of at least 10 pounds during the preceding year (J Gerontol A Biol Sci Med. 2001 Mar 1;56[3]:M146-57).

People with three or more of these conditions were identified as frail, those with one or two were tagged as prefrail, and people with none of these five characteristics were considered robust.

In the study reported by Dr. Verheij, the prevalence of people identified as robust at the time they entered the study was about 60% of those without an HIV infection and about 40% of those infected with HIV. During the 4 years she and her associates followed these people, their rates of progression from a robust state to frailty occurred more than twice as often among the people living with HIV, compared with those who were uninfected, after adjustment for age, ethnicity, and education.

Dr. Verheij admitted that she and her associates have not identified interventions that are effective for reversing frailty. “People who are already frail are likely to remain frail,” she noted. A better strategy is to take steps to defer frailty and help people who are robust retain that status. This could involve measures such as smoking cessation, exercise, and maintaining or expanding social networks, she suggested.

The AGEhiV Cohort Study enrolled 596 people living with HIV and 550 uninfected people who were all at least 45 years old. The average age was 52 years, with about 10% in each group older than 65 years. About 90% of the enrollees were Dutch, nearly three-quarters of those in both groups were men who have sex with men, and 14% of those who were uninfected and 20% of those living with HIV had symptoms of depression.

At baseline, 61% of those without HIV and 48% of people with HIV had no comorbidities, and while the percentage in both groups with one comorbidity at entry was nearly the same, 28% and 31%, respectively, the percentage with two or more comorbidities was more divergent. Among those without HIV infection, 8% had two comorbidities and 3% had three or more, while among those with HIV, 14% had two comorbidities and 6% had three or more.

The people living with HIV had been infected for an average of 12 years. At enrollment, 96% were on antiretroviral therapy, and those on treatment had received it for an average of 10 years. At enrollment, their average CD4 cell count was 565 cells/mm³. Their average nadir cell count had been 170 cells/mm³, and 32% had a history of being diagnosed with AIDS.

Dr. Verheij and her associates examined each participant at baseline and twice more, 2 and 4 years after enrollment. During the 4 years of follow-up, 17 people died. After adjustment for age, baseline comorbidities, and HIV infection, the mortality was more than 10-fold higher among people who had been frail at entry, compared with those who were robust.

During follow-up, 276 of all enrollees developed 329 comorbidities. The four most common incident comorbidities were hypertension, followed by chronic obstructive lung disease, renal insufficiency, and osteoporosis. These four conditions accounted for three-quarters of all incident comorbidities. After adjustment for demographics, baseline comorbidities, and HIV status, people who entered the study as frail or who became frail during the study had about a 90% increased rate of developing a new comorbidity compared with those who were not frail.

[email protected]

SOURCE: Verheij E et al. AIDS 2018, Abstract 9303, THAB01015.

AMSTERDAM – Middle-aged and elderly people infected with HIV were more likely to meet an established definition of frailty than were uninfected people of the same age, and during 4 years of follow-up frailty significantly linked with an increased incidence of both mortality and development of new comorbidities, based on a Dutch prospective study of 1,146 people.

Mitchel L. Zoler/MDedge News

People living with HIV also showed, despite antiretroviral treatment, a significantly increased rate of progression to frailty over the course of 4 years, compared with uninfected people, after adjustment for demographic differences. This progression to frailty appeared mediated by a high waist-to-hip ratio, a higher number of preexisting comorbidities, and symptoms of depression, Eveline Verheij, MD, said at the 22nd International AIDS Conference.

At entry into the study, people living with HIV had a 10% prevalence of frailty, compared with 3% among those who were uninfected, said Dr. Verheij, a researcher with the Amsterdam Institute for Global Health & Development. She defined frailty using criteria first introduced by researchers in 2001, which established five characteristics as markers of frailty: slow gait, low grip strength, a low level of physical activity, self-reported exhaustion, and unintentional weight loss of at least 10 pounds during the preceding year (J Gerontol A Biol Sci Med. 2001 Mar 1;56[3]:M146-57).

People with three or more of these conditions were identified as frail, those with one or two were tagged as prefrail, and people with none of these five characteristics were considered robust.

In the study reported by Dr. Verheij, the prevalence of people identified as robust at the time they entered the study was about 60% of those without an HIV infection and about 40% of those infected with HIV. During the 4 years she and her associates followed these people, their rates of progression from a robust state to frailty occurred more than twice as often among the people living with HIV, compared with those who were uninfected, after adjustment for age, ethnicity, and education.

Dr. Verheij admitted that she and her associates have not identified interventions that are effective for reversing frailty. “People who are already frail are likely to remain frail,” she noted. A better strategy is to take steps to defer frailty and help people who are robust retain that status. This could involve measures such as smoking cessation, exercise, and maintaining or expanding social networks, she suggested.

The AGEhiV Cohort Study enrolled 596 people living with HIV and 550 uninfected people who were all at least 45 years old. The average age was 52 years, with about 10% in each group older than 65 years. About 90% of the enrollees were Dutch, nearly three-quarters of those in both groups were men who have sex with men, and 14% of those who were uninfected and 20% of those living with HIV had symptoms of depression.

At baseline, 61% of those without HIV and 48% of people with HIV had no comorbidities, and while the percentage in both groups with one comorbidity at entry was nearly the same, 28% and 31%, respectively, the percentage with two or more comorbidities was more divergent. Among those without HIV infection, 8% had two comorbidities and 3% had three or more, while among those with HIV, 14% had two comorbidities and 6% had three or more.

The people living with HIV had been infected for an average of 12 years. At enrollment, 96% were on antiretroviral therapy, and those on treatment had received it for an average of 10 years. At enrollment, their average CD4 cell count was 565 cells/mm³. Their average nadir cell count had been 170 cells/mm³, and 32% had a history of being diagnosed with AIDS.

Dr. Verheij and her associates examined each participant at baseline and twice more, 2 and 4 years after enrollment. During the 4 years of follow-up, 17 people died. After adjustment for age, baseline comorbidities, and HIV infection, the mortality was more than 10-fold higher among people who had been frail at entry, compared with those who were robust.

During follow-up, 276 of all enrollees developed 329 comorbidities. The four most common incident comorbidities were hypertension, followed by chronic obstructive lung disease, renal insufficiency, and osteoporosis. These four conditions accounted for three-quarters of all incident comorbidities. After adjustment for demographics, baseline comorbidities, and HIV status, people who entered the study as frail or who became frail during the study had about a 90% increased rate of developing a new comorbidity compared with those who were not frail.

[email protected]

SOURCE: Verheij E et al. AIDS 2018, Abstract 9303, THAB01015.

Photo by Rhoda Baer

Research has shown an increase in the global incidence of leukemia and non-Hodgkin lymphoma (NHL) in recent years.

The Global Burden of Disease (GBD) study showed that, from 2006 to 2016, the incidence of NHL increased 45%, and the incidence of leukemia increased 26%.

These increases were largely due to population growth and aging.

Results from the GDB study were published in JAMA Oncology.

The study indicated that, in 2016, there were 17.2 million cases of cancer worldwide and 8.9 million cancer deaths.

One in 3 men were likely to get cancer during their lifetime, as were 1 in 5 women. Cancer was associated with 213.2 million disability-adjusted life years (DALYs).

The following table lists the 2016 global incidence and mortality figures for all cancers combined and for individual hematologic malignancies.

Leukemia

In 2016, there were 467,000 new cases of leukemia and 310,000 leukemia deaths. Leukemia was responsible for 10.2 million DALYs. Leukemia developed in 1 in 118 men and 1 in 194 women worldwide.

Between 2006 and 2016, the global leukemia incidence increased by 26%—from 370,482 to 466,802 cases.

The researchers said the factors contributing to this increase were population growth (12%), population aging (10%), and an increase in age-specific incidence rates (3%).

NHL

In 2016, there were 461,000 new cases of NHL and 240,000 NHL deaths. NHL was responsible for 6.8 million DALYs. NHL developed in 1 in 110 men and 1 in 161 women worldwide.

Between 2006 and 2016, NHL increased by 45%, from 319,078 to 461,164 cases.

The factors contributing to this increase were increasing age-specific incidence rates (17%), changing population age structure (15%), and population growth (12%).

“A large proportion of the increase in cancer incidence can be explained by improving life expectancy and population growth—a development that can at least partially be attributed to a reduced burden from other common diseases,” the study authors wrote.

The authors also pointed out that prevention efforts are less effective for hematologic malignancies than for other cancers.

Photo by Rhoda Baer

Research has shown an increase in the global incidence of leukemia and non-Hodgkin lymphoma (NHL) in recent years.

The Global Burden of Disease (GBD) study showed that, from 2006 to 2016, the incidence of NHL increased 45%, and the incidence of leukemia increased 26%.

These increases were largely due to population growth and aging.

Results from the GDB study were published in JAMA Oncology.

The study indicated that, in 2016, there were 17.2 million cases of cancer worldwide and 8.9 million cancer deaths.

One in 3 men were likely to get cancer during their lifetime, as were 1 in 5 women. Cancer was associated with 213.2 million disability-adjusted life years (DALYs).

The following table lists the 2016 global incidence and mortality figures for all cancers combined and for individual hematologic malignancies.

Leukemia

In 2016, there were 467,000 new cases of leukemia and 310,000 leukemia deaths. Leukemia was responsible for 10.2 million DALYs. Leukemia developed in 1 in 118 men and 1 in 194 women worldwide.

Between 2006 and 2016, the global leukemia incidence increased by 26%—from 370,482 to 466,802 cases.

The researchers said the factors contributing to this increase were population growth (12%), population aging (10%), and an increase in age-specific incidence rates (3%).

NHL

In 2016, there were 461,000 new cases of NHL and 240,000 NHL deaths. NHL was responsible for 6.8 million DALYs. NHL developed in 1 in 110 men and 1 in 161 women worldwide.

Between 2006 and 2016, NHL increased by 45%, from 319,078 to 461,164 cases.

The factors contributing to this increase were increasing age-specific incidence rates (17%), changing population age structure (15%), and population growth (12%).

“A large proportion of the increase in cancer incidence can be explained by improving life expectancy and population growth—a development that can at least partially be attributed to a reduced burden from other common diseases,” the study authors wrote.

The authors also pointed out that prevention efforts are less effective for hematologic malignancies than for other cancers.

Photo by Rhoda Baer

Research has shown an increase in the global incidence of leukemia and non-Hodgkin lymphoma (NHL) in recent years.

The Global Burden of Disease (GBD) study showed that, from 2006 to 2016, the incidence of NHL increased 45%, and the incidence of leukemia increased 26%.

These increases were largely due to population growth and aging.

Results from the GDB study were published in JAMA Oncology.

The study indicated that, in 2016, there were 17.2 million cases of cancer worldwide and 8.9 million cancer deaths.

One in 3 men were likely to get cancer during their lifetime, as were 1 in 5 women. Cancer was associated with 213.2 million disability-adjusted life years (DALYs).

The following table lists the 2016 global incidence and mortality figures for all cancers combined and for individual hematologic malignancies.

Leukemia

In 2016, there were 467,000 new cases of leukemia and 310,000 leukemia deaths. Leukemia was responsible for 10.2 million DALYs. Leukemia developed in 1 in 118 men and 1 in 194 women worldwide.

Between 2006 and 2016, the global leukemia incidence increased by 26%—from 370,482 to 466,802 cases.

The researchers said the factors contributing to this increase were population growth (12%), population aging (10%), and an increase in age-specific incidence rates (3%).

NHL

In 2016, there were 461,000 new cases of NHL and 240,000 NHL deaths. NHL was responsible for 6.8 million DALYs. NHL developed in 1 in 110 men and 1 in 161 women worldwide.

Between 2006 and 2016, NHL increased by 45%, from 319,078 to 461,164 cases.

The factors contributing to this increase were increasing age-specific incidence rates (17%), changing population age structure (15%), and population growth (12%).

“A large proportion of the increase in cancer incidence can be explained by improving life expectancy and population growth—a development that can at least partially be attributed to a reduced burden from other common diseases,” the study authors wrote.

The authors also pointed out that prevention efforts are less effective for hematologic malignancies than for other cancers.

The horrors faced by migrant families forced to separate under the new U.S. “zero tolerance” policy continue to unfold. Tragic emblems of this policy include tapes of crying children and the reported suicide of a father who had been separated from his children.

A federal judge had issued an injunction requiring the reunification of thousands of families by July 26. Despite that deadline, hundreds of adults are no longer in the United States, and hundreds of children are scattered in shelters across the country.

In response to those events, mental health and medical organizations have released powerful statements. The American Psychological Association stated: “The administration’s policy ... is not only needless and cruel, it threatens the mental and physical health of both the children and their caregivers.” The American Medical Association issued a call asserting that separating children from their parents “will do great harm” and “create negative health impacts that will last an individual’s entire lifespan.” Meanwhile, the American Psychiatric Association’s president, Altha J. Stewart, MD, released a statement affirming that “any forced separation is highly stressful for children and can cause lifelong trauma, as well as an increased risk of other mental illnesses, such as depression, anxiety, and posttraumatic stress disorder.”

As forensic experts who testify about the mental well-being of immigration detainees, we applaud those powerful and unambiguous messages from the leaders in our fields. Yet, their statements also underscore the limitations of our diagnostic models: Our field is caught in the difficult position of either applying ill-fitting diagnostic labels or overpathologizing a normal reaction to horrific circumstances. While not applying diagnoses potentially minimizes the enormous psychological burden of separation, diagnosing depression or PTSD as catchalls for suffering incorrectly defines the experience of many survivors of ongoing trauma.

Currently, most providers, in trying to communicate the effects of ongoing trauma, rely on the diagnoses of depression or PTSD. Both of these diagnoses, however, are problematic. The diagnosis of major depressive disorder, for example, is useful in communicating a loss of hope, and the inability to enjoy pleasurable things. However, depression is an episodic illness, often part of a larger chronic disorder.¹ Depression often has a genetic-hereditary component. On the other hand, children suffering from childhood traumas often present lifelong and wide-ranging problems, which may be triggered by reminders but are not episodic. For example, children experiencing parental separation have difficulty forming attachments, which, in turn, leads to subsequent difficulty forming meaningful interpersonal relationships.

The diagnosis of PTSD is useful in communicating a myriad of possible symptoms, which may accompany the trauma. However, PTSD implies a traumatic event as described in criteria A of the DSM-5: “exposure to actual or threatened death, serious injury, or sexual violence.” As such, PTSD poorly encompasses the wide array of smaller yet repetitive traumas experienced by victims of ongoing trauma, such as those youth separated from their parents at the U.S. border. Furthermore, PTSD is a disorder with specific symptoms that, based on a vast body of research,^2,3 inadequately describes the multitude of interpersonal, psychological, and physical consequences associated with the type of trauma caused by family separations.

Our understanding of the long-term sequelae of childhood trauma has been greatly influenced by the adverse childhood experiences (ACE) study. The ACE study, one of the largest investigations ever conducted to assess associations between childhood maltreatment and later-life health and well-being, collected the life histories of more than 17,000 patients in a collaborative effort between the Centers for Disease Control and Prevention and Kaiser Permanente’s Health Appraisal Clinic.

The ACE study identified 10 forms of childhood trauma, including: abuse, neglect, abandonment, household dysfunction, and exposure to violence, that were strongly associated with negative psychological outcomes such as depression, suicide attempts, and engagement in high-risk behaviors, as well as significant medical consequences, including higher incidence of heart disease, diabetes, and stroke. Ultimately, having four or more ACEs was associated with early death.

In response to the emerging body of research on childhood trauma, various terms, including complex trauma, type-II trauma, and complex PTSD, have entered our professional lexicon as a means of communicating the wide-ranging consequences of developmental trauma. On the one hand, the less defined and rigid nature of these terms permits mental health providers to develop a rich narrative of a patient’s background, encompassing the patient’s behavior, character, and symptoms. However, the absence of formal terminology also has its drawbacks: Courts and juries have grown accustomed to diagnoses, labels, and syndromes. Most forensic mental health providers who testify about developmental trauma in court can predict the question: “So doctor, you are saying that the individual’s presentation is not severe enough to be considered PTSD, am I correct?” Disorders justify treatment, can explain disability, and warrant empathy; concomitantly, “complex trauma” runs the risk of being considered an academic explanation for trauma victims’ lifelong problems, rather than a societal failure that merits care.

Recognizing the limitations of our current diagnoses, the forthcoming update to the International Classification of Diseases (ICD-11) will add a new category: complex PTSD. The ICD-11 will attempt to widen the concept of trauma to include “conditions of prolonged adversity, in the form of sustained, repeated, or multiple forms of traumatic exposure.” Trauma exposure examples include genocide campaigns, childhood sexual abuse, child soldiering, severe domestic violence, torture, or slavery. The ICD-11 also expands our understanding of the consequences of trauma to include “affective dysregulation,” “negative self-concept,” and “disturbances in relationships” as part of a concept called “disturbances in self-organization.” Those are important steps in acknowledging the consequences of different forms of trauma as well as noticing a richer array of damages from those incidents.⁴

While the World Health Organization’s latest iteration of the ICD takes an important step in widening the scope of our diagnostic tools, we are cognizant that our field’s obsessional search for diagnoses, labels, and nomenclature reinforces a detrimental focus on symptoms over stories. However, as forensic mental health providers, we also are keenly aware that a failure to adopt common definitions impedes forensic evaluations, patient advocacy, public policy, and most importantly, patient care.

In the end, we have trained society to understand pathology through narrow lenses, and therefore, in the face of tragic events such as family separations, we need the appropriate language to clearly define and communicate the experiences of our patients. So, despite the limitations of labels, let’s be encouraged by the World Health Organization’s efforts and continue in that direction.

 Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. Dr. Lehman is a licensed clinical and forensic psychologist in San Diego. Her practice consists of conducting forensic psychological evaluations for the courts with children, adolescents, and adults. Dr. Lehman has been qualified as an expert witness in California as well as in the federal courts. She previously was a supervisor at Sharper Future, a forensic rehabilitation program, and previously served as an adjunct faculty member at Alliant International University, San Diego. Dr. Lehman can be reached at [email protected].

References

1. Am J Psychiatry. 2000 Sep;157(9):1501-4.

2. Psychiatr Ann. 2005;35(5):390-8.

3. Psychiatr Ann. 2005;35(5):401-8.

4. Eur J Psychotraumatol. 2018 Jan 15. doi: 10.1080/20008198.2017.1418103.

The horrors faced by migrant families forced to separate under the new U.S. “zero tolerance” policy continue to unfold. Tragic emblems of this policy include tapes of crying children and the reported suicide of a father who had been separated from his children.

A federal judge had issued an injunction requiring the reunification of thousands of families by July 26. Despite that deadline, hundreds of adults are no longer in the United States, and hundreds of children are scattered in shelters across the country.

In response to those events, mental health and medical organizations have released powerful statements. The American Psychological Association stated: “The administration’s policy ... is not only needless and cruel, it threatens the mental and physical health of both the children and their caregivers.” The American Medical Association issued a call asserting that separating children from their parents “will do great harm” and “create negative health impacts that will last an individual’s entire lifespan.” Meanwhile, the American Psychiatric Association’s president, Altha J. Stewart, MD, released a statement affirming that “any forced separation is highly stressful for children and can cause lifelong trauma, as well as an increased risk of other mental illnesses, such as depression, anxiety, and posttraumatic stress disorder.”

As forensic experts who testify about the mental well-being of immigration detainees, we applaud those powerful and unambiguous messages from the leaders in our fields. Yet, their statements also underscore the limitations of our diagnostic models: Our field is caught in the difficult position of either applying ill-fitting diagnostic labels or overpathologizing a normal reaction to horrific circumstances. While not applying diagnoses potentially minimizes the enormous psychological burden of separation, diagnosing depression or PTSD as catchalls for suffering incorrectly defines the experience of many survivors of ongoing trauma.

Currently, most providers, in trying to communicate the effects of ongoing trauma, rely on the diagnoses of depression or PTSD. Both of these diagnoses, however, are problematic. The diagnosis of major depressive disorder, for example, is useful in communicating a loss of hope, and the inability to enjoy pleasurable things. However, depression is an episodic illness, often part of a larger chronic disorder.¹ Depression often has a genetic-hereditary component. On the other hand, children suffering from childhood traumas often present lifelong and wide-ranging problems, which may be triggered by reminders but are not episodic. For example, children experiencing parental separation have difficulty forming attachments, which, in turn, leads to subsequent difficulty forming meaningful interpersonal relationships.

The diagnosis of PTSD is useful in communicating a myriad of possible symptoms, which may accompany the trauma. However, PTSD implies a traumatic event as described in criteria A of the DSM-5: “exposure to actual or threatened death, serious injury, or sexual violence.” As such, PTSD poorly encompasses the wide array of smaller yet repetitive traumas experienced by victims of ongoing trauma, such as those youth separated from their parents at the U.S. border. Furthermore, PTSD is a disorder with specific symptoms that, based on a vast body of research,^2,3 inadequately describes the multitude of interpersonal, psychological, and physical consequences associated with the type of trauma caused by family separations.

Our understanding of the long-term sequelae of childhood trauma has been greatly influenced by the adverse childhood experiences (ACE) study. The ACE study, one of the largest investigations ever conducted to assess associations between childhood maltreatment and later-life health and well-being, collected the life histories of more than 17,000 patients in a collaborative effort between the Centers for Disease Control and Prevention and Kaiser Permanente’s Health Appraisal Clinic.

The ACE study identified 10 forms of childhood trauma, including: abuse, neglect, abandonment, household dysfunction, and exposure to violence, that were strongly associated with negative psychological outcomes such as depression, suicide attempts, and engagement in high-risk behaviors, as well as significant medical consequences, including higher incidence of heart disease, diabetes, and stroke. Ultimately, having four or more ACEs was associated with early death.

In response to the emerging body of research on childhood trauma, various terms, including complex trauma, type-II trauma, and complex PTSD, have entered our professional lexicon as a means of communicating the wide-ranging consequences of developmental trauma. On the one hand, the less defined and rigid nature of these terms permits mental health providers to develop a rich narrative of a patient’s background, encompassing the patient’s behavior, character, and symptoms. However, the absence of formal terminology also has its drawbacks: Courts and juries have grown accustomed to diagnoses, labels, and syndromes. Most forensic mental health providers who testify about developmental trauma in court can predict the question: “So doctor, you are saying that the individual’s presentation is not severe enough to be considered PTSD, am I correct?” Disorders justify treatment, can explain disability, and warrant empathy; concomitantly, “complex trauma” runs the risk of being considered an academic explanation for trauma victims’ lifelong problems, rather than a societal failure that merits care.

Recognizing the limitations of our current diagnoses, the forthcoming update to the International Classification of Diseases (ICD-11) will add a new category: complex PTSD. The ICD-11 will attempt to widen the concept of trauma to include “conditions of prolonged adversity, in the form of sustained, repeated, or multiple forms of traumatic exposure.” Trauma exposure examples include genocide campaigns, childhood sexual abuse, child soldiering, severe domestic violence, torture, or slavery. The ICD-11 also expands our understanding of the consequences of trauma to include “affective dysregulation,” “negative self-concept,” and “disturbances in relationships” as part of a concept called “disturbances in self-organization.” Those are important steps in acknowledging the consequences of different forms of trauma as well as noticing a richer array of damages from those incidents.⁴

While the World Health Organization’s latest iteration of the ICD takes an important step in widening the scope of our diagnostic tools, we are cognizant that our field’s obsessional search for diagnoses, labels, and nomenclature reinforces a detrimental focus on symptoms over stories. However, as forensic mental health providers, we also are keenly aware that a failure to adopt common definitions impedes forensic evaluations, patient advocacy, public policy, and most importantly, patient care.

In the end, we have trained society to understand pathology through narrow lenses, and therefore, in the face of tragic events such as family separations, we need the appropriate language to clearly define and communicate the experiences of our patients. So, despite the limitations of labels, let’s be encouraged by the World Health Organization’s efforts and continue in that direction.

 Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. Dr. Lehman is a licensed clinical and forensic psychologist in San Diego. Her practice consists of conducting forensic psychological evaluations for the courts with children, adolescents, and adults. Dr. Lehman has been qualified as an expert witness in California as well as in the federal courts. She previously was a supervisor at Sharper Future, a forensic rehabilitation program, and previously served as an adjunct faculty member at Alliant International University, San Diego. Dr. Lehman can be reached at [email protected].

References

1. Am J Psychiatry. 2000 Sep;157(9):1501-4.

2. Psychiatr Ann. 2005;35(5):390-8.

3. Psychiatr Ann. 2005;35(5):401-8.

4. Eur J Psychotraumatol. 2018 Jan 15. doi: 10.1080/20008198.2017.1418103.

The horrors faced by migrant families forced to separate under the new U.S. “zero tolerance” policy continue to unfold. Tragic emblems of this policy include tapes of crying children and the reported suicide of a father who had been separated from his children.

A federal judge had issued an injunction requiring the reunification of thousands of families by July 26. Despite that deadline, hundreds of adults are no longer in the United States, and hundreds of children are scattered in shelters across the country.

In response to those events, mental health and medical organizations have released powerful statements. The American Psychological Association stated: “The administration’s policy ... is not only needless and cruel, it threatens the mental and physical health of both the children and their caregivers.” The American Medical Association issued a call asserting that separating children from their parents “will do great harm” and “create negative health impacts that will last an individual’s entire lifespan.” Meanwhile, the American Psychiatric Association’s president, Altha J. Stewart, MD, released a statement affirming that “any forced separation is highly stressful for children and can cause lifelong trauma, as well as an increased risk of other mental illnesses, such as depression, anxiety, and posttraumatic stress disorder.”

As forensic experts who testify about the mental well-being of immigration detainees, we applaud those powerful and unambiguous messages from the leaders in our fields. Yet, their statements also underscore the limitations of our diagnostic models: Our field is caught in the difficult position of either applying ill-fitting diagnostic labels or overpathologizing a normal reaction to horrific circumstances. While not applying diagnoses potentially minimizes the enormous psychological burden of separation, diagnosing depression or PTSD as catchalls for suffering incorrectly defines the experience of many survivors of ongoing trauma.

Currently, most providers, in trying to communicate the effects of ongoing trauma, rely on the diagnoses of depression or PTSD. Both of these diagnoses, however, are problematic. The diagnosis of major depressive disorder, for example, is useful in communicating a loss of hope, and the inability to enjoy pleasurable things. However, depression is an episodic illness, often part of a larger chronic disorder.¹ Depression often has a genetic-hereditary component. On the other hand, children suffering from childhood traumas often present lifelong and wide-ranging problems, which may be triggered by reminders but are not episodic. For example, children experiencing parental separation have difficulty forming attachments, which, in turn, leads to subsequent difficulty forming meaningful interpersonal relationships.

The diagnosis of PTSD is useful in communicating a myriad of possible symptoms, which may accompany the trauma. However, PTSD implies a traumatic event as described in criteria A of the DSM-5: “exposure to actual or threatened death, serious injury, or sexual violence.” As such, PTSD poorly encompasses the wide array of smaller yet repetitive traumas experienced by victims of ongoing trauma, such as those youth separated from their parents at the U.S. border. Furthermore, PTSD is a disorder with specific symptoms that, based on a vast body of research,^2,3 inadequately describes the multitude of interpersonal, psychological, and physical consequences associated with the type of trauma caused by family separations.

Our understanding of the long-term sequelae of childhood trauma has been greatly influenced by the adverse childhood experiences (ACE) study. The ACE study, one of the largest investigations ever conducted to assess associations between childhood maltreatment and later-life health and well-being, collected the life histories of more than 17,000 patients in a collaborative effort between the Centers for Disease Control and Prevention and Kaiser Permanente’s Health Appraisal Clinic.

The ACE study identified 10 forms of childhood trauma, including: abuse, neglect, abandonment, household dysfunction, and exposure to violence, that were strongly associated with negative psychological outcomes such as depression, suicide attempts, and engagement in high-risk behaviors, as well as significant medical consequences, including higher incidence of heart disease, diabetes, and stroke. Ultimately, having four or more ACEs was associated with early death.

In response to the emerging body of research on childhood trauma, various terms, including complex trauma, type-II trauma, and complex PTSD, have entered our professional lexicon as a means of communicating the wide-ranging consequences of developmental trauma. On the one hand, the less defined and rigid nature of these terms permits mental health providers to develop a rich narrative of a patient’s background, encompassing the patient’s behavior, character, and symptoms. However, the absence of formal terminology also has its drawbacks: Courts and juries have grown accustomed to diagnoses, labels, and syndromes. Most forensic mental health providers who testify about developmental trauma in court can predict the question: “So doctor, you are saying that the individual’s presentation is not severe enough to be considered PTSD, am I correct?” Disorders justify treatment, can explain disability, and warrant empathy; concomitantly, “complex trauma” runs the risk of being considered an academic explanation for trauma victims’ lifelong problems, rather than a societal failure that merits care.

Recognizing the limitations of our current diagnoses, the forthcoming update to the International Classification of Diseases (ICD-11) will add a new category: complex PTSD. The ICD-11 will attempt to widen the concept of trauma to include “conditions of prolonged adversity, in the form of sustained, repeated, or multiple forms of traumatic exposure.” Trauma exposure examples include genocide campaigns, childhood sexual abuse, child soldiering, severe domestic violence, torture, or slavery. The ICD-11 also expands our understanding of the consequences of trauma to include “affective dysregulation,” “negative self-concept,” and “disturbances in relationships” as part of a concept called “disturbances in self-organization.” Those are important steps in acknowledging the consequences of different forms of trauma as well as noticing a richer array of damages from those incidents.⁴

While the World Health Organization’s latest iteration of the ICD takes an important step in widening the scope of our diagnostic tools, we are cognizant that our field’s obsessional search for diagnoses, labels, and nomenclature reinforces a detrimental focus on symptoms over stories. However, as forensic mental health providers, we also are keenly aware that a failure to adopt common definitions impedes forensic evaluations, patient advocacy, public policy, and most importantly, patient care.

In the end, we have trained society to understand pathology through narrow lenses, and therefore, in the face of tragic events such as family separations, we need the appropriate language to clearly define and communicate the experiences of our patients. So, despite the limitations of labels, let’s be encouraged by the World Health Organization’s efforts and continue in that direction.

 Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. Dr. Lehman is a licensed clinical and forensic psychologist in San Diego. Her practice consists of conducting forensic psychological evaluations for the courts with children, adolescents, and adults. Dr. Lehman has been qualified as an expert witness in California as well as in the federal courts. She previously was a supervisor at Sharper Future, a forensic rehabilitation program, and previously served as an adjunct faculty member at Alliant International University, San Diego. Dr. Lehman can be reached at [email protected].

References

1. Am J Psychiatry. 2000 Sep;157(9):1501-4.

2. Psychiatr Ann. 2005;35(5):390-8.

3. Psychiatr Ann. 2005;35(5):401-8.

4. Eur J Psychotraumatol. 2018 Jan 15. doi: 10.1080/20008198.2017.1418103.

Circulating tumor cells could be used to stratify patients with hormone receptor (HR)–positive, HER2-negative breast cancer for late recurrence risk, results of a secondary analysis of a randomized clinical trial suggest.

Risk of late clinical recurrence was about 13-fold higher among HR-positive patients with a positive circulating tumor cell (CTC) assay result, according to results of the study, published in JAMA Oncology.

“This prospectively conducted study offers a high level of evidence supporting the association between a positive CTC assay result and risk of clinical recurrence,” said Joseph A. Sparano, MD, of Albert Einstein College of Medicine, New York, and his coauthors.

The present study is the first to show that this CTC assay may play a role in determining late clinical recurrence after local and systemic adjuvant therapy, according to the investigators. The assay (CellSearch) is cleared by the Food and Drug Administration for enumeration of CTCs in patients with metastatic breast cancer.

The study is a secondary analysis of E5103, a phase 3 trial of adjuvant doxorubicin and cyclophosphamide followed by paclitaxel with bevacizumab in patients with HER2-negative stage II-III breast cancer. Investigators included a total of 547 patients who had no clinical evidence of recurrence between 4.5 and 7.5 years of registration in that trial.

Positive CTC assay results occurred in 26 of those patients (4.8%), they found.

At a median follow-up of 2.6 years, 24 patients had a clinical recurrence, including 23 HR-positive patients and just 1 HR-negative patient. Accordingly, the investigators focused most of their further analysis on the HR-positive subset.

A total of 7 of 23 patients with HR-positive disease (30.4%) had a positive CTC assay result.

A positive CTC result in HR-positive patients was associated with a 13.1-fold increased risk of recurrence, multivariate analysis showed.

Higher CTC burden appeared to be associated with a numerically higher recurrence risk in HR-positive patients, the investigators found. They saw recurrences in 16 of 335 patients with a CTC count of 0 cells per 7.5 mL blood (4.8%), compared with 2 of 12 patients with 1 cell per 7.5 mL blood (16.7%), and 5 of 6 patients with 2 or more cells per 7.5 mL (83.3%).

Taken together, these results provided proof of concept to support additional investigations of the CTC assay and other blood-based biomarker tests in the setting of late clinical recurrence in HR-positive patients, the researchers said.

They acknowledged several limitations of this study: It was small, it had relatively short follow-up, and it did not evaluate the CTC assay in the context of other assays.

“Notwithstanding proof of concept, further evaluation is required to confirm the clinical validity and determine the clinical utility of performing the CTC assay in this context,” Dr. Sparano and his coauthors wrote.

Late recurrences, or those that occur more than 5 years after diagnosis, account for about half of all recurrences among HR-positive receptive breast cancers, Dr. Sparano and his colleagues said.

The researchers had no conflicts of interest to report. The study was supported by grants from the National Cancer Institute, National Institutes of Health, Breast Cancer Research Foundation, and Susan G. Komen Foundation.

SOURCE: Sparano J et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2574.

Circulating tumor cells could be used to stratify patients with hormone receptor (HR)–positive, HER2-negative breast cancer for late recurrence risk, results of a secondary analysis of a randomized clinical trial suggest.

Risk of late clinical recurrence was about 13-fold higher among HR-positive patients with a positive circulating tumor cell (CTC) assay result, according to results of the study, published in JAMA Oncology.

“This prospectively conducted study offers a high level of evidence supporting the association between a positive CTC assay result and risk of clinical recurrence,” said Joseph A. Sparano, MD, of Albert Einstein College of Medicine, New York, and his coauthors.

The present study is the first to show that this CTC assay may play a role in determining late clinical recurrence after local and systemic adjuvant therapy, according to the investigators. The assay (CellSearch) is cleared by the Food and Drug Administration for enumeration of CTCs in patients with metastatic breast cancer.

The study is a secondary analysis of E5103, a phase 3 trial of adjuvant doxorubicin and cyclophosphamide followed by paclitaxel with bevacizumab in patients with HER2-negative stage II-III breast cancer. Investigators included a total of 547 patients who had no clinical evidence of recurrence between 4.5 and 7.5 years of registration in that trial.

Positive CTC assay results occurred in 26 of those patients (4.8%), they found.

At a median follow-up of 2.6 years, 24 patients had a clinical recurrence, including 23 HR-positive patients and just 1 HR-negative patient. Accordingly, the investigators focused most of their further analysis on the HR-positive subset.

A total of 7 of 23 patients with HR-positive disease (30.4%) had a positive CTC assay result.

A positive CTC result in HR-positive patients was associated with a 13.1-fold increased risk of recurrence, multivariate analysis showed.

Higher CTC burden appeared to be associated with a numerically higher recurrence risk in HR-positive patients, the investigators found. They saw recurrences in 16 of 335 patients with a CTC count of 0 cells per 7.5 mL blood (4.8%), compared with 2 of 12 patients with 1 cell per 7.5 mL blood (16.7%), and 5 of 6 patients with 2 or more cells per 7.5 mL (83.3%).

Taken together, these results provided proof of concept to support additional investigations of the CTC assay and other blood-based biomarker tests in the setting of late clinical recurrence in HR-positive patients, the researchers said.

They acknowledged several limitations of this study: It was small, it had relatively short follow-up, and it did not evaluate the CTC assay in the context of other assays.

“Notwithstanding proof of concept, further evaluation is required to confirm the clinical validity and determine the clinical utility of performing the CTC assay in this context,” Dr. Sparano and his coauthors wrote.

Late recurrences, or those that occur more than 5 years after diagnosis, account for about half of all recurrences among HR-positive receptive breast cancers, Dr. Sparano and his colleagues said.

The researchers had no conflicts of interest to report. The study was supported by grants from the National Cancer Institute, National Institutes of Health, Breast Cancer Research Foundation, and Susan G. Komen Foundation.

SOURCE: Sparano J et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2574.

Circulating tumor cells could be used to stratify patients with hormone receptor (HR)–positive, HER2-negative breast cancer for late recurrence risk, results of a secondary analysis of a randomized clinical trial suggest.

Risk of late clinical recurrence was about 13-fold higher among HR-positive patients with a positive circulating tumor cell (CTC) assay result, according to results of the study, published in JAMA Oncology.

“This prospectively conducted study offers a high level of evidence supporting the association between a positive CTC assay result and risk of clinical recurrence,” said Joseph A. Sparano, MD, of Albert Einstein College of Medicine, New York, and his coauthors.

The present study is the first to show that this CTC assay may play a role in determining late clinical recurrence after local and systemic adjuvant therapy, according to the investigators. The assay (CellSearch) is cleared by the Food and Drug Administration for enumeration of CTCs in patients with metastatic breast cancer.

The study is a secondary analysis of E5103, a phase 3 trial of adjuvant doxorubicin and cyclophosphamide followed by paclitaxel with bevacizumab in patients with HER2-negative stage II-III breast cancer. Investigators included a total of 547 patients who had no clinical evidence of recurrence between 4.5 and 7.5 years of registration in that trial.

Positive CTC assay results occurred in 26 of those patients (4.8%), they found.

At a median follow-up of 2.6 years, 24 patients had a clinical recurrence, including 23 HR-positive patients and just 1 HR-negative patient. Accordingly, the investigators focused most of their further analysis on the HR-positive subset.

A total of 7 of 23 patients with HR-positive disease (30.4%) had a positive CTC assay result.

A positive CTC result in HR-positive patients was associated with a 13.1-fold increased risk of recurrence, multivariate analysis showed.

Higher CTC burden appeared to be associated with a numerically higher recurrence risk in HR-positive patients, the investigators found. They saw recurrences in 16 of 335 patients with a CTC count of 0 cells per 7.5 mL blood (4.8%), compared with 2 of 12 patients with 1 cell per 7.5 mL blood (16.7%), and 5 of 6 patients with 2 or more cells per 7.5 mL (83.3%).

Taken together, these results provided proof of concept to support additional investigations of the CTC assay and other blood-based biomarker tests in the setting of late clinical recurrence in HR-positive patients, the researchers said.

They acknowledged several limitations of this study: It was small, it had relatively short follow-up, and it did not evaluate the CTC assay in the context of other assays.

“Notwithstanding proof of concept, further evaluation is required to confirm the clinical validity and determine the clinical utility of performing the CTC assay in this context,” Dr. Sparano and his coauthors wrote.

Late recurrences, or those that occur more than 5 years after diagnosis, account for about half of all recurrences among HR-positive receptive breast cancers, Dr. Sparano and his colleagues said.

The researchers had no conflicts of interest to report. The study was supported by grants from the National Cancer Institute, National Institutes of Health, Breast Cancer Research Foundation, and Susan G. Komen Foundation.

SOURCE: Sparano J et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2574.

Children who undergo allogeneic blood or marrow transplantation (BMT) remain at an elevated risk of premature death even 25 years after the procedure, results of large, retrospective cohort study suggest.

Despite a significant decrease over several decades, the risk of all-cause mortality remained elevated, compared with the general population, according to this study of individuals who had BMT performed in childhood between 1974 and 2010.

“These findings emphasize the need for lifelong follow-up care after allogeneic BMT performed in childhood,” reported Anna Sällfors Holmqvist, MD, PhD, of the department of clinical sciences at Skåne University Hospital, Lund University, Sweden, and her associates.

Screening, preventive care, and counseling need to be part of that long-term follow-up, Dr. Holmqvist and her colleagues reported in JAMA Oncology.

Their retrospective analysis included 1,388 individuals who lived at least 2 years after allogeneic BMT performed in childhood at one of three centers: the University of Alabama at Birmingham; the University of Minnesota, Minneapolis; and City of Hope, Duarte, Calif.

There were 295 deaths over a median of 14.9 years of follow-up, for an overall survival rate of 79.3% at 20 years after BMT, reported Dr. Holmqvist and her associates. The three leading causes of death were infection or chronic graft-versus-host disease in 49.6% of cases, primary disease in 24.6%, and later malignancies in 18.4%.

Relative to the general population, the cohort had a 14.4-fold increased risk of premature death (95% confidence interval, 12.8-16.1), compared with the general population. Relative mortality was highest 2-5 years after BMT and dropped substantially after that but remained elevated – even 25 years or more after the procedure, the investigators noted.

Mortality decreased significantly over the 3 decades evaluated in this study. The rate of all-cause, 10-year cumulative mortality was 18.9% before 1990, 12.9% from 1990 to 1999, and 11.0% from 2000 to 2010 (P = .002).

That decrease in cumulative mortality over time could not be explained by changes in transplant practice over those three time periods, according to results of a mediation analysis performed by Dr. Holmqvist and her associates.

That finding suggests that unmeasured variables might underlie the decrease in late mortality, the investigators said.

Those unmeasured variables might include supportive care strategies, management of chronic graft-versus-host disease, or improved patient selection, they noted.

Dr. Holmqvist and her associates cited as one limitation their reliance on death certificates for causes of death. In addition, the causes of death for 51 of the 295 deceased patients were lacking.

The study was supported in part by grants from the National Cancer Institute, the Leukemia Lymphoma Society, and the Swedish Childhood Cancer Foundation. Dr. Holmqvist and her associates reported no conflicts of interest.

SOURCE: Holmqvist AS et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2453.

Children who undergo allogeneic blood or marrow transplantation (BMT) remain at an elevated risk of premature death even 25 years after the procedure, results of large, retrospective cohort study suggest.

Despite a significant decrease over several decades, the risk of all-cause mortality remained elevated, compared with the general population, according to this study of individuals who had BMT performed in childhood between 1974 and 2010.

“These findings emphasize the need for lifelong follow-up care after allogeneic BMT performed in childhood,” reported Anna Sällfors Holmqvist, MD, PhD, of the department of clinical sciences at Skåne University Hospital, Lund University, Sweden, and her associates.

Screening, preventive care, and counseling need to be part of that long-term follow-up, Dr. Holmqvist and her colleagues reported in JAMA Oncology.

Their retrospective analysis included 1,388 individuals who lived at least 2 years after allogeneic BMT performed in childhood at one of three centers: the University of Alabama at Birmingham; the University of Minnesota, Minneapolis; and City of Hope, Duarte, Calif.

There were 295 deaths over a median of 14.9 years of follow-up, for an overall survival rate of 79.3% at 20 years after BMT, reported Dr. Holmqvist and her associates. The three leading causes of death were infection or chronic graft-versus-host disease in 49.6% of cases, primary disease in 24.6%, and later malignancies in 18.4%.

Relative to the general population, the cohort had a 14.4-fold increased risk of premature death (95% confidence interval, 12.8-16.1), compared with the general population. Relative mortality was highest 2-5 years after BMT and dropped substantially after that but remained elevated – even 25 years or more after the procedure, the investigators noted.

Mortality decreased significantly over the 3 decades evaluated in this study. The rate of all-cause, 10-year cumulative mortality was 18.9% before 1990, 12.9% from 1990 to 1999, and 11.0% from 2000 to 2010 (P = .002).

That decrease in cumulative mortality over time could not be explained by changes in transplant practice over those three time periods, according to results of a mediation analysis performed by Dr. Holmqvist and her associates.

That finding suggests that unmeasured variables might underlie the decrease in late mortality, the investigators said.

Those unmeasured variables might include supportive care strategies, management of chronic graft-versus-host disease, or improved patient selection, they noted.

Dr. Holmqvist and her associates cited as one limitation their reliance on death certificates for causes of death. In addition, the causes of death for 51 of the 295 deceased patients were lacking.

The study was supported in part by grants from the National Cancer Institute, the Leukemia Lymphoma Society, and the Swedish Childhood Cancer Foundation. Dr. Holmqvist and her associates reported no conflicts of interest.

SOURCE: Holmqvist AS et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2453.

Children who undergo allogeneic blood or marrow transplantation (BMT) remain at an elevated risk of premature death even 25 years after the procedure, results of large, retrospective cohort study suggest.

Despite a significant decrease over several decades, the risk of all-cause mortality remained elevated, compared with the general population, according to this study of individuals who had BMT performed in childhood between 1974 and 2010.

“These findings emphasize the need for lifelong follow-up care after allogeneic BMT performed in childhood,” reported Anna Sällfors Holmqvist, MD, PhD, of the department of clinical sciences at Skåne University Hospital, Lund University, Sweden, and her associates.

Screening, preventive care, and counseling need to be part of that long-term follow-up, Dr. Holmqvist and her colleagues reported in JAMA Oncology.

Their retrospective analysis included 1,388 individuals who lived at least 2 years after allogeneic BMT performed in childhood at one of three centers: the University of Alabama at Birmingham; the University of Minnesota, Minneapolis; and City of Hope, Duarte, Calif.

There were 295 deaths over a median of 14.9 years of follow-up, for an overall survival rate of 79.3% at 20 years after BMT, reported Dr. Holmqvist and her associates. The three leading causes of death were infection or chronic graft-versus-host disease in 49.6% of cases, primary disease in 24.6%, and later malignancies in 18.4%.

Relative to the general population, the cohort had a 14.4-fold increased risk of premature death (95% confidence interval, 12.8-16.1), compared with the general population. Relative mortality was highest 2-5 years after BMT and dropped substantially after that but remained elevated – even 25 years or more after the procedure, the investigators noted.

Mortality decreased significantly over the 3 decades evaluated in this study. The rate of all-cause, 10-year cumulative mortality was 18.9% before 1990, 12.9% from 1990 to 1999, and 11.0% from 2000 to 2010 (P = .002).

That decrease in cumulative mortality over time could not be explained by changes in transplant practice over those three time periods, according to results of a mediation analysis performed by Dr. Holmqvist and her associates.

That finding suggests that unmeasured variables might underlie the decrease in late mortality, the investigators said.

Those unmeasured variables might include supportive care strategies, management of chronic graft-versus-host disease, or improved patient selection, they noted.

Dr. Holmqvist and her associates cited as one limitation their reliance on death certificates for causes of death. In addition, the causes of death for 51 of the 295 deceased patients were lacking.

The study was supported in part by grants from the National Cancer Institute, the Leukemia Lymphoma Society, and the Swedish Childhood Cancer Foundation. Dr. Holmqvist and her associates reported no conflicts of interest.

SOURCE: Holmqvist AS et al. JAMA Oncol. 2018 Jul 26. doi: 10.1001/jamaoncol.2018.2453.

CHICAGO – When a child or adolescent comes to the dermatologist’s office with a concern about fingernails or toenails, physician antennae may go up. “The world is different in the world of pediatrics – and even in the world of adolescents,” said Sheila Fallon Friedlander, MD.

In adults, the most common cause of nail dystrophy is tinea, but for younger pediatric patients, less than 1% of nail problems are attributable to fungus, so dermatologists may need to look further.

“It’s so important in kids to do a good history and physical exam,” said Dr. Friedlander, professor of dermatology and pediatrics at the University of California, San Diego. History-taking should include determining whether the condition has been present since birth and how nail appearance has changed over time.

For Dr. Friedlander, the approach to nail abnormalities includes a full head and skin exam. “I always look at the teeth, the hair, the skin,” she said; underlying bony anomalies also may surface. A complete exam often will turn up important clues if a syndrome underpins the nail abnormalities, she said, speaking at the American Academy of Dermatology summer meeting.

Her exemplar patient, she said, is a 19-year-old male who comes in with a parent because he’s bothered by his fingernails, which are dystrophic and small. A head-to-toe exam shows micronychia of both toes and fingers, with lunulae that are triangularly shaped. The hair, skin, and teeth of the patient all were normal in appearance. However, “The knees and elbows were odd,” Dr. Friedlander said.

This patient has nail-patella syndrome. “Even though it’s rare, I want you to think about it,” Dr. Friedlander said. The autosomal dominant condition is seen in about 1 in 50,000 patients. It’s thought to be caused by heterozygous loss-of-function mutations in gene LMX1B, she said, that codes for a LIM homeobox transcription factor 1 beta.

Though the small nails and triangular lunulae may be what brings the patient to the dermatologist’s office, a careful exam and one radiograph can pick up a tetrad of anomalies, Dr. Friedlander said. Abnormalities can be seen in both the knees and elbows; the patellae are often small, and may even be absent. In addition, a hip radiograph will show characteristic “horns” on the posterior iliac crests.

Coming back to the dermatologic exam, Dr. Friedlander said nails may be absent, hypoplastic, and dystrophic – but those are features that can be shared with other nail disorders, inherited and acquired. The pathognomonic finding for nail-patella syndrome is the presence of the triangular lunula, she said.

Now that the diagnosis has been made, Dr. Friedlander asked about this young man: “Where will you refer him?” Knowing the diagnosis means that there are a lot of calls for your staff to make, she said.

The patient with knee patella syndrome should be referred to an orthopedist to assess knees and elbows; radial head subluxation also is common in these patients, she said.

An ophthalmologic referral is important as well; hyperpigmentation of the pupillary margin – a “Lester iris” – can be seen, and increased rates of cataracts and glaucoma also are associated with nail-patella syndrome.

“The message I want you to leave with is that these kids need to be seen by a nephrologist,” Dr. Friedlander said. Up to half of nail-patella syndrome patients will have kidney involvement that initially presents with hematuria and proteinuria. Because the LMX1B mutation impairs how podocytes and glomerular filtration slits develop and function, up to 10% can develop end-stage renal failure, she said.

Parents also should be on the lookout for associated behavioral issues: “The other thing that’s interesting is that these kids have an increased risk of [attention-deficit/hyperactivity disorder] and major depression,” Dr. Friedlander said.

Dr. Friedlander reported that she had no relevant conflicts of interest.

[email protected]

SOURCE: Friedlander, S. Summer AAD 2018. Session F004.

CHICAGO – When a child or adolescent comes to the dermatologist’s office with a concern about fingernails or toenails, physician antennae may go up. “The world is different in the world of pediatrics – and even in the world of adolescents,” said Sheila Fallon Friedlander, MD.

In adults, the most common cause of nail dystrophy is tinea, but for younger pediatric patients, less than 1% of nail problems are attributable to fungus, so dermatologists may need to look further.

“It’s so important in kids to do a good history and physical exam,” said Dr. Friedlander, professor of dermatology and pediatrics at the University of California, San Diego. History-taking should include determining whether the condition has been present since birth and how nail appearance has changed over time.

For Dr. Friedlander, the approach to nail abnormalities includes a full head and skin exam. “I always look at the teeth, the hair, the skin,” she said; underlying bony anomalies also may surface. A complete exam often will turn up important clues if a syndrome underpins the nail abnormalities, she said, speaking at the American Academy of Dermatology summer meeting.

Her exemplar patient, she said, is a 19-year-old male who comes in with a parent because he’s bothered by his fingernails, which are dystrophic and small. A head-to-toe exam shows micronychia of both toes and fingers, with lunulae that are triangularly shaped. The hair, skin, and teeth of the patient all were normal in appearance. However, “The knees and elbows were odd,” Dr. Friedlander said.

This patient has nail-patella syndrome. “Even though it’s rare, I want you to think about it,” Dr. Friedlander said. The autosomal dominant condition is seen in about 1 in 50,000 patients. It’s thought to be caused by heterozygous loss-of-function mutations in gene LMX1B, she said, that codes for a LIM homeobox transcription factor 1 beta.

Though the small nails and triangular lunulae may be what brings the patient to the dermatologist’s office, a careful exam and one radiograph can pick up a tetrad of anomalies, Dr. Friedlander said. Abnormalities can be seen in both the knees and elbows; the patellae are often small, and may even be absent. In addition, a hip radiograph will show characteristic “horns” on the posterior iliac crests.

Coming back to the dermatologic exam, Dr. Friedlander said nails may be absent, hypoplastic, and dystrophic – but those are features that can be shared with other nail disorders, inherited and acquired. The pathognomonic finding for nail-patella syndrome is the presence of the triangular lunula, she said.

Now that the diagnosis has been made, Dr. Friedlander asked about this young man: “Where will you refer him?” Knowing the diagnosis means that there are a lot of calls for your staff to make, she said.

The patient with knee patella syndrome should be referred to an orthopedist to assess knees and elbows; radial head subluxation also is common in these patients, she said.

An ophthalmologic referral is important as well; hyperpigmentation of the pupillary margin – a “Lester iris” – can be seen, and increased rates of cataracts and glaucoma also are associated with nail-patella syndrome.

“The message I want you to leave with is that these kids need to be seen by a nephrologist,” Dr. Friedlander said. Up to half of nail-patella syndrome patients will have kidney involvement that initially presents with hematuria and proteinuria. Because the LMX1B mutation impairs how podocytes and glomerular filtration slits develop and function, up to 10% can develop end-stage renal failure, she said.

Parents also should be on the lookout for associated behavioral issues: “The other thing that’s interesting is that these kids have an increased risk of [attention-deficit/hyperactivity disorder] and major depression,” Dr. Friedlander said.

Dr. Friedlander reported that she had no relevant conflicts of interest.

[email protected]

SOURCE: Friedlander, S. Summer AAD 2018. Session F004.

CHICAGO – When a child or adolescent comes to the dermatologist’s office with a concern about fingernails or toenails, physician antennae may go up. “The world is different in the world of pediatrics – and even in the world of adolescents,” said Sheila Fallon Friedlander, MD.

In adults, the most common cause of nail dystrophy is tinea, but for younger pediatric patients, less than 1% of nail problems are attributable to fungus, so dermatologists may need to look further.

“It’s so important in kids to do a good history and physical exam,” said Dr. Friedlander, professor of dermatology and pediatrics at the University of California, San Diego. History-taking should include determining whether the condition has been present since birth and how nail appearance has changed over time.

For Dr. Friedlander, the approach to nail abnormalities includes a full head and skin exam. “I always look at the teeth, the hair, the skin,” she said; underlying bony anomalies also may surface. A complete exam often will turn up important clues if a syndrome underpins the nail abnormalities, she said, speaking at the American Academy of Dermatology summer meeting.

Her exemplar patient, she said, is a 19-year-old male who comes in with a parent because he’s bothered by his fingernails, which are dystrophic and small. A head-to-toe exam shows micronychia of both toes and fingers, with lunulae that are triangularly shaped. The hair, skin, and teeth of the patient all were normal in appearance. However, “The knees and elbows were odd,” Dr. Friedlander said.

This patient has nail-patella syndrome. “Even though it’s rare, I want you to think about it,” Dr. Friedlander said. The autosomal dominant condition is seen in about 1 in 50,000 patients. It’s thought to be caused by heterozygous loss-of-function mutations in gene LMX1B, she said, that codes for a LIM homeobox transcription factor 1 beta.

Though the small nails and triangular lunulae may be what brings the patient to the dermatologist’s office, a careful exam and one radiograph can pick up a tetrad of anomalies, Dr. Friedlander said. Abnormalities can be seen in both the knees and elbows; the patellae are often small, and may even be absent. In addition, a hip radiograph will show characteristic “horns” on the posterior iliac crests.

Coming back to the dermatologic exam, Dr. Friedlander said nails may be absent, hypoplastic, and dystrophic – but those are features that can be shared with other nail disorders, inherited and acquired. The pathognomonic finding for nail-patella syndrome is the presence of the triangular lunula, she said.

Now that the diagnosis has been made, Dr. Friedlander asked about this young man: “Where will you refer him?” Knowing the diagnosis means that there are a lot of calls for your staff to make, she said.

The patient with knee patella syndrome should be referred to an orthopedist to assess knees and elbows; radial head subluxation also is common in these patients, she said.

An ophthalmologic referral is important as well; hyperpigmentation of the pupillary margin – a “Lester iris” – can be seen, and increased rates of cataracts and glaucoma also are associated with nail-patella syndrome.

“The message I want you to leave with is that these kids need to be seen by a nephrologist,” Dr. Friedlander said. Up to half of nail-patella syndrome patients will have kidney involvement that initially presents with hematuria and proteinuria. Because the LMX1B mutation impairs how podocytes and glomerular filtration slits develop and function, up to 10% can develop end-stage renal failure, she said.

Parents also should be on the lookout for associated behavioral issues: “The other thing that’s interesting is that these kids have an increased risk of [attention-deficit/hyperactivity disorder] and major depression,” Dr. Friedlander said.

Dr. Friedlander reported that she had no relevant conflicts of interest.

[email protected]

SOURCE: Friedlander, S. Summer AAD 2018. Session F004.

ATLANTA – An adjustment in the culture reporting schedule at Texas Children’s Hospital, Houston, helped reduce the average length of stay for neonatal fever from 48 to 43 hours, without increasing readmissions for serious bacterial infections, according to a review presented at the Pediatric Hospital Medicine meeting.

M. Alexander Otto/MDedge News

Investigators there were working to meet the goals of the Reducing Excessive Variability in Infant Sepsis Evaluation project (REVISE), a national collaboration aimed at improving care. One of the goals is to reduce the length of stay (LOS) for neonatal fever to fewer than 30 hours for low-risk infants and fewer than 42 hours among high-risk infants.

The traditional standard is to keep children in the hospital for 48 hours to rule out sepsis, but that thinking has begun to change amid evidence that blood cultures generally do not need that long to turn positive, among other findings, said investigator Huay-Ying Lo, MD, a pediatrician at Texas Children’s.

“At our institution,” which admits more than 200 NF cases annually, “we have order sets for neonatal fever, and we’re actually doing pretty well” meeting most of the REVISE goals, “so we decided to focus on reducing length of stay,” she said at the meeting.

Evidence of the safety and cost savings of earlier discharge was presented to providers, and weekly emails reminded them of the early discharge goal and updated them on the current average LOS for NF.

Dr. Lo and her team also brainstormed with providers to identify problems. “One of the barriers they consistently mentioned was the timing of cultures being reported out from the microbiology lab. A lot of time, people were just waiting for the report to say no growth for 36 hours or whatever it was going to be,” she said.

That led to talks with the microbiology department. Blood cultures were already automated, so there wasn’t much that needed to be done. Urine cultures were read manually three to four times a day after the initial incubation period. However, after an initial Gram stain, CSF cultures were read manually only one or two times a day – whenever somebody had time. The hours were random, and sometimes results were not reported until the evening, which meant the child had to spend another night in the hospital.

The lab director agreed that it was a problem, and standardized procedures to read cultures twice a day, at 7 a.m. and 2 p.m. “The times we agreed upon; 7 a.m. works really well for morning discharge, and at 2 p.m., the day team is still there and can get kids out that day,” Dr. Lo explained.

Along with staff education and LOS reporting, timely culture reports made a difference. Among infants 7-60 days old admitted with NF – excluding ill-appearing children and those with comorbidities that increased the risk of infections – the mean LOS fell from 48 hours among 144 infants treated before the intervention, to 43 hours among 157 treated afterward (P = .001), and “we didn’t have any more readmission for serious bacterial infections,” Dr. Lo said.

“We want to reduce it further. If we get to 42 hours, we’ll be pretty happy.” Updating discharge criteria, and letting providers know how their LOS’s compare with their peers’ might help. “I’m sure some people are more conservative and some a little more liberal,” she said.

There was no industry funding for the work, and the investigators had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

ATLANTA – An adjustment in the culture reporting schedule at Texas Children’s Hospital, Houston, helped reduce the average length of stay for neonatal fever from 48 to 43 hours, without increasing readmissions for serious bacterial infections, according to a review presented at the Pediatric Hospital Medicine meeting.

M. Alexander Otto/MDedge News

Investigators there were working to meet the goals of the Reducing Excessive Variability in Infant Sepsis Evaluation project (REVISE), a national collaboration aimed at improving care. One of the goals is to reduce the length of stay (LOS) for neonatal fever to fewer than 30 hours for low-risk infants and fewer than 42 hours among high-risk infants.

The traditional standard is to keep children in the hospital for 48 hours to rule out sepsis, but that thinking has begun to change amid evidence that blood cultures generally do not need that long to turn positive, among other findings, said investigator Huay-Ying Lo, MD, a pediatrician at Texas Children’s.

“At our institution,” which admits more than 200 NF cases annually, “we have order sets for neonatal fever, and we’re actually doing pretty well” meeting most of the REVISE goals, “so we decided to focus on reducing length of stay,” she said at the meeting.

Evidence of the safety and cost savings of earlier discharge was presented to providers, and weekly emails reminded them of the early discharge goal and updated them on the current average LOS for NF.

Dr. Lo and her team also brainstormed with providers to identify problems. “One of the barriers they consistently mentioned was the timing of cultures being reported out from the microbiology lab. A lot of time, people were just waiting for the report to say no growth for 36 hours or whatever it was going to be,” she said.

That led to talks with the microbiology department. Blood cultures were already automated, so there wasn’t much that needed to be done. Urine cultures were read manually three to four times a day after the initial incubation period. However, after an initial Gram stain, CSF cultures were read manually only one or two times a day – whenever somebody had time. The hours were random, and sometimes results were not reported until the evening, which meant the child had to spend another night in the hospital.

The lab director agreed that it was a problem, and standardized procedures to read cultures twice a day, at 7 a.m. and 2 p.m. “The times we agreed upon; 7 a.m. works really well for morning discharge, and at 2 p.m., the day team is still there and can get kids out that day,” Dr. Lo explained.

Along with staff education and LOS reporting, timely culture reports made a difference. Among infants 7-60 days old admitted with NF – excluding ill-appearing children and those with comorbidities that increased the risk of infections – the mean LOS fell from 48 hours among 144 infants treated before the intervention, to 43 hours among 157 treated afterward (P = .001), and “we didn’t have any more readmission for serious bacterial infections,” Dr. Lo said.

“We want to reduce it further. If we get to 42 hours, we’ll be pretty happy.” Updating discharge criteria, and letting providers know how their LOS’s compare with their peers’ might help. “I’m sure some people are more conservative and some a little more liberal,” she said.

There was no industry funding for the work, and the investigators had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

ATLANTA – An adjustment in the culture reporting schedule at Texas Children’s Hospital, Houston, helped reduce the average length of stay for neonatal fever from 48 to 43 hours, without increasing readmissions for serious bacterial infections, according to a review presented at the Pediatric Hospital Medicine meeting.

M. Alexander Otto/MDedge News

Investigators there were working to meet the goals of the Reducing Excessive Variability in Infant Sepsis Evaluation project (REVISE), a national collaboration aimed at improving care. One of the goals is to reduce the length of stay (LOS) for neonatal fever to fewer than 30 hours for low-risk infants and fewer than 42 hours among high-risk infants.

The traditional standard is to keep children in the hospital for 48 hours to rule out sepsis, but that thinking has begun to change amid evidence that blood cultures generally do not need that long to turn positive, among other findings, said investigator Huay-Ying Lo, MD, a pediatrician at Texas Children’s.

“At our institution,” which admits more than 200 NF cases annually, “we have order sets for neonatal fever, and we’re actually doing pretty well” meeting most of the REVISE goals, “so we decided to focus on reducing length of stay,” she said at the meeting.

Evidence of the safety and cost savings of earlier discharge was presented to providers, and weekly emails reminded them of the early discharge goal and updated them on the current average LOS for NF.

Dr. Lo and her team also brainstormed with providers to identify problems. “One of the barriers they consistently mentioned was the timing of cultures being reported out from the microbiology lab. A lot of time, people were just waiting for the report to say no growth for 36 hours or whatever it was going to be,” she said.

That led to talks with the microbiology department. Blood cultures were already automated, so there wasn’t much that needed to be done. Urine cultures were read manually three to four times a day after the initial incubation period. However, after an initial Gram stain, CSF cultures were read manually only one or two times a day – whenever somebody had time. The hours were random, and sometimes results were not reported until the evening, which meant the child had to spend another night in the hospital.

The lab director agreed that it was a problem, and standardized procedures to read cultures twice a day, at 7 a.m. and 2 p.m. “The times we agreed upon; 7 a.m. works really well for morning discharge, and at 2 p.m., the day team is still there and can get kids out that day,” Dr. Lo explained.

Along with staff education and LOS reporting, timely culture reports made a difference. Among infants 7-60 days old admitted with NF – excluding ill-appearing children and those with comorbidities that increased the risk of infections – the mean LOS fell from 48 hours among 144 infants treated before the intervention, to 43 hours among 157 treated afterward (P = .001), and “we didn’t have any more readmission for serious bacterial infections,” Dr. Lo said.

“We want to reduce it further. If we get to 42 hours, we’ll be pretty happy.” Updating discharge criteria, and letting providers know how their LOS’s compare with their peers’ might help. “I’m sure some people are more conservative and some a little more liberal,” she said.

There was no industry funding for the work, and the investigators had no disclosures. The meeting was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, and the Academic Pediatric Association.

[email protected]

The risk of cancer from N-nitrosodimethylamine (NDMA) contained in impure valsartan is real but very low, the Food and Drug Administration said in a July 27 statement.

The agency had announced a voluntary recall of valsartan from Major Pharmaceuticals, Solco Healthcare, and Teva Pharmaceuticals, as well as valsartan/hydrochlorothiazide from Solco and Teva, on July 13 after detection of NDMA, a semi-volatile organic compound. The manufacturer, Zhejiang Huahai Pharmaceuticals in Linhai, China, has since stopped distribution. Contamination probably is tied to a change in the manufacturing process.

NDMA has been linked to cancer in animal studies but at levels “much higher than the impurity levels in recalled valsartan batches.” Even so, the agency “wanted to put some context around the actual potential risk posed to patients who used versions of valsartan that may have contained high levels of NDMA,” the FDA said in its updated press release.

Based on records from the manufacturer, “some levels of the impurity may have been in the valsartan-containing products for as long as 4 years. FDA scientists estimate that if 8,000 people took the highest valsartan dose (320 mg) from the recalled batches daily for the full 4 years, there may be one additional case of cancer over the lifetimes of these 8,000 people,” the agency said.

“To put this in context, currently one out of every three people in the U.S. will experience cancer in their lifetime,” it said.

The FDA advised patients to check their prescriptions to see if they originate from one of the recalled batches, and to let their doctors and pharmacists know if they are.

To help, the FDA has posted a list of products included in the recall and a list of products not included in the recall.

Patients taking recalled valsartan should continue taking it until given a replacement. They should also follow the recall instructions provided by the specific companies, the FDA said.

[email protected]

The risk of cancer from N-nitrosodimethylamine (NDMA) contained in impure valsartan is real but very low, the Food and Drug Administration said in a July 27 statement.

The agency had announced a voluntary recall of valsartan from Major Pharmaceuticals, Solco Healthcare, and Teva Pharmaceuticals, as well as valsartan/hydrochlorothiazide from Solco and Teva, on July 13 after detection of NDMA, a semi-volatile organic compound. The manufacturer, Zhejiang Huahai Pharmaceuticals in Linhai, China, has since stopped distribution. Contamination probably is tied to a change in the manufacturing process.

NDMA has been linked to cancer in animal studies but at levels “much higher than the impurity levels in recalled valsartan batches.” Even so, the agency “wanted to put some context around the actual potential risk posed to patients who used versions of valsartan that may have contained high levels of NDMA,” the FDA said in its updated press release.

Based on records from the manufacturer, “some levels of the impurity may have been in the valsartan-containing products for as long as 4 years. FDA scientists estimate that if 8,000 people took the highest valsartan dose (320 mg) from the recalled batches daily for the full 4 years, there may be one additional case of cancer over the lifetimes of these 8,000 people,” the agency said.

“To put this in context, currently one out of every three people in the U.S. will experience cancer in their lifetime,” it said.

The FDA advised patients to check their prescriptions to see if they originate from one of the recalled batches, and to let their doctors and pharmacists know if they are.

To help, the FDA has posted a list of products included in the recall and a list of products not included in the recall.

Patients taking recalled valsartan should continue taking it until given a replacement. They should also follow the recall instructions provided by the specific companies, the FDA said.

[email protected]

The risk of cancer from N-nitrosodimethylamine (NDMA) contained in impure valsartan is real but very low, the Food and Drug Administration said in a July 27 statement.

The agency had announced a voluntary recall of valsartan from Major Pharmaceuticals, Solco Healthcare, and Teva Pharmaceuticals, as well as valsartan/hydrochlorothiazide from Solco and Teva, on July 13 after detection of NDMA, a semi-volatile organic compound. The manufacturer, Zhejiang Huahai Pharmaceuticals in Linhai, China, has since stopped distribution. Contamination probably is tied to a change in the manufacturing process.

NDMA has been linked to cancer in animal studies but at levels “much higher than the impurity levels in recalled valsartan batches.” Even so, the agency “wanted to put some context around the actual potential risk posed to patients who used versions of valsartan that may have contained high levels of NDMA,” the FDA said in its updated press release.

Based on records from the manufacturer, “some levels of the impurity may have been in the valsartan-containing products for as long as 4 years. FDA scientists estimate that if 8,000 people took the highest valsartan dose (320 mg) from the recalled batches daily for the full 4 years, there may be one additional case of cancer over the lifetimes of these 8,000 people,” the agency said.

“To put this in context, currently one out of every three people in the U.S. will experience cancer in their lifetime,” it said.

The FDA advised patients to check their prescriptions to see if they originate from one of the recalled batches, and to let their doctors and pharmacists know if they are.

To help, the FDA has posted a list of products included in the recall and a list of products not included in the recall.

Patients taking recalled valsartan should continue taking it until given a replacement. They should also follow the recall instructions provided by the specific companies, the FDA said.

[email protected]

PARIS – The Synergy bioabsorbable polymer everolimus-eluting stent performed equally well for treatment of acute MI, compared with other newer-generation drug-eluting stents, through 2 years of follow-up in a massive observational study of all patients undergoing percutaneous coronary intervention in Sweden during a recent multiyear period.

Bruce Jancin/MDedge News

This report from the prospective Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was undertaken because, even though the Synergy stent has demonstrated outstanding clinical results in randomized trials and observational studies, the stent’s performance specifically in the setting of acute MI had not previously been investigated, Sergio Buccheri, MD, noted at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

SCAAR, which documents every PCI performed in Sweden, provided the capability to fill that important knowledge gap in an unselected real-world population of acute MI patients. Dr. Buccheri, of Uppsala (Sweden) University, reported on 36,292 consecutive patients who underwent PCI with a newer-generation drug-eluting stent (DES) in Sweden from March 2013 to September 2016. Forty percent of them had ST-elevation MI. The Synergy stent was used in 4,889 patients. Among the most commonly used newer DES in the other 31,000-plus patients were the Xience Xpedition, the Resolute Integrity and Resolute Onyx, the Orsiro, BioMatrix, and Promus Element Plus and Promus Premier.

The coprimary endpoints in this analysis were the rates of definite stent thrombosis and clinically relevant restenosis at 2 years of follow-up. Stent thrombosis occurred in 0.69% of the Synergy patients and 0.81% of those who received other newer-generation DES, a nonsignificant difference. Similarly, no significant difference was found in the rate of clinically relevant restenosis: 1.48% and 1.25%, respectively.

“The rates of stent thrombosis and restenosis were reassuringly low with both Synergy and other newer-DES devices,” Dr. Buccheri noted. “These findings may be useful to support a more informed and evidence-based stent selection process in daily clinical practice.”

The key secondary outcomes were all-cause mortality and recurrent MI. Again, there were no significant between-group differences. The cumulative all-cause mortality at 2 years was 10.1% in the Synergy group and 9.1% in the others. Recurrent MI occurred in 6.49% of the Synergy group and 6.32% with other DES.

Patients who received the Synergy stent were on average older, had a higher burden of cardiovascular risk factors, and presented more often with left main, triple-vessel disease or vein graft lesions. For that reason, Dr. Buccheri and his coinvestigators developed a propensity score using an array of covariates to adjust for these differences. Plugging those scores into multivariate Cox regression models, there remained no significant differences between the two groups in the adjusted risk of any of the endpoints.

Operators were advised to use dual antiplatelet therapy for 12 months in all patients. However, SCAAR does not include data on adherence to DAPT, which is a study limitation, Dr. Buccheri noted.

The Synergy stent is made up of a thin strut chromium-platinum platform with a bioabsorbable polymer that releases everolimus. The polymer is completely reabsorbed within 4 months, leaving behind a bare metal stent. In animal models, this has been associated with lower levels of inflammation, compared with permanent polymer DES. And inflammation is thought to be one of the main mechanisms underlying stent failure in the late and very late phases after PCI.

The discussion panel was clearly impressed with – and envious of – the sheer size of the SCAAR study population. As one panelist noted, real-life data of this magnitude can really only be obtained in Sweden. Another panelist confessed: “We’re shy of presenting our own studies when we see these numbers.”

Simultaneously with Dr. Buccheri’s presentation, the SCAAR report was published online (EuroIntervention. 2018 May 24. pii: EIJ-D-18-00392. doi: 10.4244/EIJ-D-18-00392).

SCAAR is funded solely by the Swedish government. This study was supported by a grant from Boston Scientific. Dr. Buccheri reported having no financial conflicts of interest.

[email protected]

PARIS – The Synergy bioabsorbable polymer everolimus-eluting stent performed equally well for treatment of acute MI, compared with other newer-generation drug-eluting stents, through 2 years of follow-up in a massive observational study of all patients undergoing percutaneous coronary intervention in Sweden during a recent multiyear period.

Bruce Jancin/MDedge News

This report from the prospective Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was undertaken because, even though the Synergy stent has demonstrated outstanding clinical results in randomized trials and observational studies, the stent’s performance specifically in the setting of acute MI had not previously been investigated, Sergio Buccheri, MD, noted at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

SCAAR, which documents every PCI performed in Sweden, provided the capability to fill that important knowledge gap in an unselected real-world population of acute MI patients. Dr. Buccheri, of Uppsala (Sweden) University, reported on 36,292 consecutive patients who underwent PCI with a newer-generation drug-eluting stent (DES) in Sweden from March 2013 to September 2016. Forty percent of them had ST-elevation MI. The Synergy stent was used in 4,889 patients. Among the most commonly used newer DES in the other 31,000-plus patients were the Xience Xpedition, the Resolute Integrity and Resolute Onyx, the Orsiro, BioMatrix, and Promus Element Plus and Promus Premier.

The coprimary endpoints in this analysis were the rates of definite stent thrombosis and clinically relevant restenosis at 2 years of follow-up. Stent thrombosis occurred in 0.69% of the Synergy patients and 0.81% of those who received other newer-generation DES, a nonsignificant difference. Similarly, no significant difference was found in the rate of clinically relevant restenosis: 1.48% and 1.25%, respectively.

“The rates of stent thrombosis and restenosis were reassuringly low with both Synergy and other newer-DES devices,” Dr. Buccheri noted. “These findings may be useful to support a more informed and evidence-based stent selection process in daily clinical practice.”

The key secondary outcomes were all-cause mortality and recurrent MI. Again, there were no significant between-group differences. The cumulative all-cause mortality at 2 years was 10.1% in the Synergy group and 9.1% in the others. Recurrent MI occurred in 6.49% of the Synergy group and 6.32% with other DES.

Patients who received the Synergy stent were on average older, had a higher burden of cardiovascular risk factors, and presented more often with left main, triple-vessel disease or vein graft lesions. For that reason, Dr. Buccheri and his coinvestigators developed a propensity score using an array of covariates to adjust for these differences. Plugging those scores into multivariate Cox regression models, there remained no significant differences between the two groups in the adjusted risk of any of the endpoints.

Operators were advised to use dual antiplatelet therapy for 12 months in all patients. However, SCAAR does not include data on adherence to DAPT, which is a study limitation, Dr. Buccheri noted.

The Synergy stent is made up of a thin strut chromium-platinum platform with a bioabsorbable polymer that releases everolimus. The polymer is completely reabsorbed within 4 months, leaving behind a bare metal stent. In animal models, this has been associated with lower levels of inflammation, compared with permanent polymer DES. And inflammation is thought to be one of the main mechanisms underlying stent failure in the late and very late phases after PCI.

The discussion panel was clearly impressed with – and envious of – the sheer size of the SCAAR study population. As one panelist noted, real-life data of this magnitude can really only be obtained in Sweden. Another panelist confessed: “We’re shy of presenting our own studies when we see these numbers.”

Simultaneously with Dr. Buccheri’s presentation, the SCAAR report was published online (EuroIntervention. 2018 May 24. pii: EIJ-D-18-00392. doi: 10.4244/EIJ-D-18-00392).

SCAAR is funded solely by the Swedish government. This study was supported by a grant from Boston Scientific. Dr. Buccheri reported having no financial conflicts of interest.

[email protected]

PARIS – The Synergy bioabsorbable polymer everolimus-eluting stent performed equally well for treatment of acute MI, compared with other newer-generation drug-eluting stents, through 2 years of follow-up in a massive observational study of all patients undergoing percutaneous coronary intervention in Sweden during a recent multiyear period.

Bruce Jancin/MDedge News

This report from the prospective Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was undertaken because, even though the Synergy stent has demonstrated outstanding clinical results in randomized trials and observational studies, the stent’s performance specifically in the setting of acute MI had not previously been investigated, Sergio Buccheri, MD, noted at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

SCAAR, which documents every PCI performed in Sweden, provided the capability to fill that important knowledge gap in an unselected real-world population of acute MI patients. Dr. Buccheri, of Uppsala (Sweden) University, reported on 36,292 consecutive patients who underwent PCI with a newer-generation drug-eluting stent (DES) in Sweden from March 2013 to September 2016. Forty percent of them had ST-elevation MI. The Synergy stent was used in 4,889 patients. Among the most commonly used newer DES in the other 31,000-plus patients were the Xience Xpedition, the Resolute Integrity and Resolute Onyx, the Orsiro, BioMatrix, and Promus Element Plus and Promus Premier.

The coprimary endpoints in this analysis were the rates of definite stent thrombosis and clinically relevant restenosis at 2 years of follow-up. Stent thrombosis occurred in 0.69% of the Synergy patients and 0.81% of those who received other newer-generation DES, a nonsignificant difference. Similarly, no significant difference was found in the rate of clinically relevant restenosis: 1.48% and 1.25%, respectively.

“The rates of stent thrombosis and restenosis were reassuringly low with both Synergy and other newer-DES devices,” Dr. Buccheri noted. “These findings may be useful to support a more informed and evidence-based stent selection process in daily clinical practice.”

The key secondary outcomes were all-cause mortality and recurrent MI. Again, there were no significant between-group differences. The cumulative all-cause mortality at 2 years was 10.1% in the Synergy group and 9.1% in the others. Recurrent MI occurred in 6.49% of the Synergy group and 6.32% with other DES.

Patients who received the Synergy stent were on average older, had a higher burden of cardiovascular risk factors, and presented more often with left main, triple-vessel disease or vein graft lesions. For that reason, Dr. Buccheri and his coinvestigators developed a propensity score using an array of covariates to adjust for these differences. Plugging those scores into multivariate Cox regression models, there remained no significant differences between the two groups in the adjusted risk of any of the endpoints.

Operators were advised to use dual antiplatelet therapy for 12 months in all patients. However, SCAAR does not include data on adherence to DAPT, which is a study limitation, Dr. Buccheri noted.

The Synergy stent is made up of a thin strut chromium-platinum platform with a bioabsorbable polymer that releases everolimus. The polymer is completely reabsorbed within 4 months, leaving behind a bare metal stent. In animal models, this has been associated with lower levels of inflammation, compared with permanent polymer DES. And inflammation is thought to be one of the main mechanisms underlying stent failure in the late and very late phases after PCI.

The discussion panel was clearly impressed with – and envious of – the sheer size of the SCAAR study population. As one panelist noted, real-life data of this magnitude can really only be obtained in Sweden. Another panelist confessed: “We’re shy of presenting our own studies when we see these numbers.”

Simultaneously with Dr. Buccheri’s presentation, the SCAAR report was published online (EuroIntervention. 2018 May 24. pii: EIJ-D-18-00392. doi: 10.4244/EIJ-D-18-00392).

SCAAR is funded solely by the Swedish government. This study was supported by a grant from Boston Scientific. Dr. Buccheri reported having no financial conflicts of interest.

[email protected]