User login
CCSs have increased risk of hypertension
A study of childhood cancer survivors (CCSs) suggests these individuals have an increased risk of developing hypertension as adults.
The CCSs studied had more than double the rate of hypertension observed in the matched general population.
Sex, age, race, and weight were all significantly associated with hypertension among CCSs, but most treatment types were not.
The exception was nephrectomy, which was associated with an increased risk of hypertension.
Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted this research and reported the results in Cancer Epidemiology, Biomarkers & Prevention.
“High blood pressure is an important modifiable risk factor that increases the risk of heart problems in everyone,” Dr Gibson said. “Research has shown that high blood pressure can have an even greater negative impact on survivors of childhood cancer who were treated with cardiotoxic therapies such as anthracyclines or chest radiation.”
To assess the prevalence of hypertension among CCSs, Dr Gibson and his colleagues examined 3016 adults who were 10-year survivors of childhood cancers. The subjects were enrolled in the St. Jude Lifetime Cohort Study, which provides ongoing medical assessments of CCSs to advance knowledge of their long-term health outcomes.
The subjects’ mean age at the initial study assessment was 32, and 52% were male. Most (83%) were non-Hispanic white, 14% were non-Hispanic black, 2% were Hispanic, and 1% were “other.”
Thirty-seven percent of subjects had leukemia, 12% had Hodgkin lymphoma, and 7% had non-Hodgkin lymphoma.
Eighty-six percent of subjects had received chemotherapy, and 59% received radiation.
Results
Subjects were considered to have hypertension if their systolic blood pressure was 140 or greater, their diastolic blood pressure was 90 or greater, or if they had been previously diagnosed with hypertension and were taking antihypertensive medication.
The prevalence of hypertension was 2.6 times higher among CCSs than expected, based on age-, sex-, race- and body mass index-specific rates in the general population.
In addition, the incidence of hypertension increased for CCSs over time. Thirteen percent of CCSs had hypertension at age 30, 37% had it at age 40, and more than 70% had it at age 50.
Dr Gibson said rates of hypertension in CCSs matched rates in the general population of people about a decade older.
The researchers identified several factors that were significantly associated with hypertension among CCSs, including:
- Male sex (odd ratio [OR], 1.38; 95% CI, 1.14–1.67)
- Non-Hispanic black race (OR, 1.66; 95% CI, 1.28–2.16)
- Older age at assessment (OR per 1 year of age, 1.10; 95% CI, 1.08–1.11)
- Being overweight (OR, 1.58; 95% CI, 1.21–2.07)
- Obesity (OR, 3.02; 95% CI, 2.34–3.88).
Exposure to any type of radiation or chemotherapy was not significantly associated with hypertension, but nephrectomy was (OR, 1.68; 95% CI, 1.11–2.53).
Dr Gibson said the lack of an association between hypertension and radiation/chemotherapy was surprising. It suggests the connection between childhood cancer survival and adult hypertension is multifactorial and worthy of future research.
In the meantime, he said, clinicians should be mindful that CCSs are more likely than the general public to develop hypertension.
“The good news is that, unlike prior cancer therapy, high blood pressure is a modifiable risk factor,” Dr Gibson noted. “Research is needed to identify effective interventions to prevent hypertension in survivors, but our results emphasize the importance of blood pressure surveillance and management.”
Dr Gibson said a limitation of this study is that it was based on blood pressure measurements taken at a single study visit. A clinical diagnosis of hypertension typically requires measurements taken at multiple intervals.
In addition, the St. Jude Lifetime Cohort is a group of CCSs who undergo frequent clinical follow-up, so its participants may have benefited from being monitored and may therefore be in better health than CCSs who have less comprehensive follow-up. 
A study of childhood cancer survivors (CCSs) suggests these individuals have an increased risk of developing hypertension as adults.
The CCSs studied had more than double the rate of hypertension observed in the matched general population.
Sex, age, race, and weight were all significantly associated with hypertension among CCSs, but most treatment types were not.
The exception was nephrectomy, which was associated with an increased risk of hypertension.
Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted this research and reported the results in Cancer Epidemiology, Biomarkers & Prevention.
“High blood pressure is an important modifiable risk factor that increases the risk of heart problems in everyone,” Dr Gibson said. “Research has shown that high blood pressure can have an even greater negative impact on survivors of childhood cancer who were treated with cardiotoxic therapies such as anthracyclines or chest radiation.”
To assess the prevalence of hypertension among CCSs, Dr Gibson and his colleagues examined 3016 adults who were 10-year survivors of childhood cancers. The subjects were enrolled in the St. Jude Lifetime Cohort Study, which provides ongoing medical assessments of CCSs to advance knowledge of their long-term health outcomes.
The subjects’ mean age at the initial study assessment was 32, and 52% were male. Most (83%) were non-Hispanic white, 14% were non-Hispanic black, 2% were Hispanic, and 1% were “other.”
Thirty-seven percent of subjects had leukemia, 12% had Hodgkin lymphoma, and 7% had non-Hodgkin lymphoma.
Eighty-six percent of subjects had received chemotherapy, and 59% received radiation.
Results
Subjects were considered to have hypertension if their systolic blood pressure was 140 or greater, their diastolic blood pressure was 90 or greater, or if they had been previously diagnosed with hypertension and were taking antihypertensive medication.
The prevalence of hypertension was 2.6 times higher among CCSs than expected, based on age-, sex-, race- and body mass index-specific rates in the general population.
In addition, the incidence of hypertension increased for CCSs over time. Thirteen percent of CCSs had hypertension at age 30, 37% had it at age 40, and more than 70% had it at age 50.
Dr Gibson said rates of hypertension in CCSs matched rates in the general population of people about a decade older.
The researchers identified several factors that were significantly associated with hypertension among CCSs, including:
- Male sex (odd ratio [OR], 1.38; 95% CI, 1.14–1.67)
- Non-Hispanic black race (OR, 1.66; 95% CI, 1.28–2.16)
- Older age at assessment (OR per 1 year of age, 1.10; 95% CI, 1.08–1.11)
- Being overweight (OR, 1.58; 95% CI, 1.21–2.07)
- Obesity (OR, 3.02; 95% CI, 2.34–3.88).
Exposure to any type of radiation or chemotherapy was not significantly associated with hypertension, but nephrectomy was (OR, 1.68; 95% CI, 1.11–2.53).
Dr Gibson said the lack of an association between hypertension and radiation/chemotherapy was surprising. It suggests the connection between childhood cancer survival and adult hypertension is multifactorial and worthy of future research.
In the meantime, he said, clinicians should be mindful that CCSs are more likely than the general public to develop hypertension.
“The good news is that, unlike prior cancer therapy, high blood pressure is a modifiable risk factor,” Dr Gibson noted. “Research is needed to identify effective interventions to prevent hypertension in survivors, but our results emphasize the importance of blood pressure surveillance and management.”
Dr Gibson said a limitation of this study is that it was based on blood pressure measurements taken at a single study visit. A clinical diagnosis of hypertension typically requires measurements taken at multiple intervals.
In addition, the St. Jude Lifetime Cohort is a group of CCSs who undergo frequent clinical follow-up, so its participants may have benefited from being monitored and may therefore be in better health than CCSs who have less comprehensive follow-up.
A study of childhood cancer survivors (CCSs) suggests these individuals have an increased risk of developing hypertension as adults.
The CCSs studied had more than double the rate of hypertension observed in the matched general population.
Sex, age, race, and weight were all significantly associated with hypertension among CCSs, but most treatment types were not.
The exception was nephrectomy, which was associated with an increased risk of hypertension.
Todd M. Gibson, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues conducted this research and reported the results in Cancer Epidemiology, Biomarkers & Prevention.
“High blood pressure is an important modifiable risk factor that increases the risk of heart problems in everyone,” Dr Gibson said. “Research has shown that high blood pressure can have an even greater negative impact on survivors of childhood cancer who were treated with cardiotoxic therapies such as anthracyclines or chest radiation.”
To assess the prevalence of hypertension among CCSs, Dr Gibson and his colleagues examined 3016 adults who were 10-year survivors of childhood cancers. The subjects were enrolled in the St. Jude Lifetime Cohort Study, which provides ongoing medical assessments of CCSs to advance knowledge of their long-term health outcomes.
The subjects’ mean age at the initial study assessment was 32, and 52% were male. Most (83%) were non-Hispanic white, 14% were non-Hispanic black, 2% were Hispanic, and 1% were “other.”
Thirty-seven percent of subjects had leukemia, 12% had Hodgkin lymphoma, and 7% had non-Hodgkin lymphoma.
Eighty-six percent of subjects had received chemotherapy, and 59% received radiation.
Results
Subjects were considered to have hypertension if their systolic blood pressure was 140 or greater, their diastolic blood pressure was 90 or greater, or if they had been previously diagnosed with hypertension and were taking antihypertensive medication.
The prevalence of hypertension was 2.6 times higher among CCSs than expected, based on age-, sex-, race- and body mass index-specific rates in the general population.
In addition, the incidence of hypertension increased for CCSs over time. Thirteen percent of CCSs had hypertension at age 30, 37% had it at age 40, and more than 70% had it at age 50.
Dr Gibson said rates of hypertension in CCSs matched rates in the general population of people about a decade older.
The researchers identified several factors that were significantly associated with hypertension among CCSs, including:
- Male sex (odd ratio [OR], 1.38; 95% CI, 1.14–1.67)
- Non-Hispanic black race (OR, 1.66; 95% CI, 1.28–2.16)
- Older age at assessment (OR per 1 year of age, 1.10; 95% CI, 1.08–1.11)
- Being overweight (OR, 1.58; 95% CI, 1.21–2.07)
- Obesity (OR, 3.02; 95% CI, 2.34–3.88).
Exposure to any type of radiation or chemotherapy was not significantly associated with hypertension, but nephrectomy was (OR, 1.68; 95% CI, 1.11–2.53).
Dr Gibson said the lack of an association between hypertension and radiation/chemotherapy was surprising. It suggests the connection between childhood cancer survival and adult hypertension is multifactorial and worthy of future research.
In the meantime, he said, clinicians should be mindful that CCSs are more likely than the general public to develop hypertension.
“The good news is that, unlike prior cancer therapy, high blood pressure is a modifiable risk factor,” Dr Gibson noted. “Research is needed to identify effective interventions to prevent hypertension in survivors, but our results emphasize the importance of blood pressure surveillance and management.”
Dr Gibson said a limitation of this study is that it was based on blood pressure measurements taken at a single study visit. A clinical diagnosis of hypertension typically requires measurements taken at multiple intervals.
In addition, the St. Jude Lifetime Cohort is a group of CCSs who undergo frequent clinical follow-up, so its participants may have benefited from being monitored and may therefore be in better health than CCSs who have less comprehensive follow-up.
Race may transcend social, geographical parameters in lupus mortality
SAN DIEGO – Blacks with systemic lupus erythematosus (SLE) who share the same social and geographic contexts as whites with the disease were disproportionately more likely to die young and to show severe patterns of mortality, according to a study of death certificate data.
“One of the most salient aspects of the epidemiology of lupus is the predilection of the disease for women and racial minorities,” lead study author Titilola Falasinnu, PhD, said at the annual meeting of the American College of Rheumatology.
Dr. Falasinnu, a postdoctoral fellow in Stanford (Calif.) University’s department of health research and policy, and her associates examined SLE mortality across eight groups of race-county combinations published in 2006 and known as the “Eight Americas” (PLoS Med. 2006 Sep 12;3[9]:e260). This seminal work, which has been validated across multiple disease states, jointly characterized race, socioeconomic status, and geographical location in relation to health disparities in the United States to demonstrate the most important factors accounting for these disparities within the Eight Americas.
For the current analysis, Dr. Falasinnu and her associates were most interested in America 6 (black middle America), America 7 (Southern low-income rural blacks), and America 8 (high-risk urban blacks). “The question we wanted to ask is whether, on average, poorer individuals have more severe SLE mortality experiences, compared with richer individuals in the black community,” she said. “What happens when you hold race constant and you vary socioeconomic indices?” Using death certificate data from the National Center for Health Statistics Multiple Causes of Death database, they identified SLE-related deaths between 2003 and 2014. Next, they compared these data with mortality statistics from each of the Eight Americas.
In all, there were nearly 25,000 SLE-related deaths, of which 85% were female. More than one-third of deaths occurred among those aged 45-64 years, and the mean age at death was 57 years. More than half of deaths (64%) occurred among whites, and 31% among blacks. Among SLE decedents, northern rural whites in America 2 had the lowest mortality rates. Blacks in America 6, 7, and 8 had the highest mortality, yet there were no significant differences in the death rates among those three groups. “We found that in general, blacks were three times more likely to die with SLE, compared with those in America 3 [middle America],” Dr. Falasinnu said.
Asians, Native Americans, and blacks with SLE died at an average age of 48-49 years, regardless of their social context, while Northern whites had the highest life expectancy: an average age of 69 years. They also found that 17% of SLE deaths in America 2 occurred before the age of 50 years, compared with more than 50% in Americas 6, 7, and 8. The most frequently reported associated causes of death were cardiovascular disease (about 50% of all SLE-related deaths) and kidney manifestations (about 20% of all SLE-related deaths). Compared with those in America 3, racial minorities had a 23%-53% higher risk of infections, a 5%-64% higher risk of kidney disease, a 7%-23% lower risk of cardiovascular disease, and a 20%-52% lower risk of cancers.
“Although blacks inhabited three vastly different geographical and social contexts, SLE mortality parameters did not vary among socially advantaged and disadvantaged black Americas,” Dr. Falasinnu concluded. “Blacks sharing the same social and geographical contexts as whites were disproportionately more likely to die young and exhibit patterns of mortality associated with active SLE disease.”
She acknowledged certain limitations of the study, including that differences in the degree of underreporting on death certificates across racial groups could bias the results. “The Eight Americas framework does not allow for evaluation of ethnicity,” she added. “We were also unable to examine causes for the disparities in SLE mortality. One could argue that there are a lot of other social factors that are likely race related that are not necessarily captured by the Eight Americas. Also, as with most epidemiological studies, we cannot rule out the role that ecological fallacy may play where the population average may not be appropriate in estimating an individual’s risk of mortality.”
One of the study coauthors reported receiving partial salary support through the Dr. Elaine Lambert Lupus Foundation via the John and Marcia Goldman Foundation and previously receiving salary support through a lupus-related grant from the Genomics Institute of the Novartis Research Foundation. The other coauthors reported having no relevant disclosures.
[email protected]
SAN DIEGO – Blacks with systemic lupus erythematosus (SLE) who share the same social and geographic contexts as whites with the disease were disproportionately more likely to die young and to show severe patterns of mortality, according to a study of death certificate data.
“One of the most salient aspects of the epidemiology of lupus is the predilection of the disease for women and racial minorities,” lead study author Titilola Falasinnu, PhD, said at the annual meeting of the American College of Rheumatology.
Dr. Falasinnu, a postdoctoral fellow in Stanford (Calif.) University’s department of health research and policy, and her associates examined SLE mortality across eight groups of race-county combinations published in 2006 and known as the “Eight Americas” (PLoS Med. 2006 Sep 12;3[9]:e260). This seminal work, which has been validated across multiple disease states, jointly characterized race, socioeconomic status, and geographical location in relation to health disparities in the United States to demonstrate the most important factors accounting for these disparities within the Eight Americas.
For the current analysis, Dr. Falasinnu and her associates were most interested in America 6 (black middle America), America 7 (Southern low-income rural blacks), and America 8 (high-risk urban blacks). “The question we wanted to ask is whether, on average, poorer individuals have more severe SLE mortality experiences, compared with richer individuals in the black community,” she said. “What happens when you hold race constant and you vary socioeconomic indices?” Using death certificate data from the National Center for Health Statistics Multiple Causes of Death database, they identified SLE-related deaths between 2003 and 2014. Next, they compared these data with mortality statistics from each of the Eight Americas.
In all, there were nearly 25,000 SLE-related deaths, of which 85% were female. More than one-third of deaths occurred among those aged 45-64 years, and the mean age at death was 57 years. More than half of deaths (64%) occurred among whites, and 31% among blacks. Among SLE decedents, northern rural whites in America 2 had the lowest mortality rates. Blacks in America 6, 7, and 8 had the highest mortality, yet there were no significant differences in the death rates among those three groups. “We found that in general, blacks were three times more likely to die with SLE, compared with those in America 3 [middle America],” Dr. Falasinnu said.
Asians, Native Americans, and blacks with SLE died at an average age of 48-49 years, regardless of their social context, while Northern whites had the highest life expectancy: an average age of 69 years. They also found that 17% of SLE deaths in America 2 occurred before the age of 50 years, compared with more than 50% in Americas 6, 7, and 8. The most frequently reported associated causes of death were cardiovascular disease (about 50% of all SLE-related deaths) and kidney manifestations (about 20% of all SLE-related deaths). Compared with those in America 3, racial minorities had a 23%-53% higher risk of infections, a 5%-64% higher risk of kidney disease, a 7%-23% lower risk of cardiovascular disease, and a 20%-52% lower risk of cancers.
“Although blacks inhabited three vastly different geographical and social contexts, SLE mortality parameters did not vary among socially advantaged and disadvantaged black Americas,” Dr. Falasinnu concluded. “Blacks sharing the same social and geographical contexts as whites were disproportionately more likely to die young and exhibit patterns of mortality associated with active SLE disease.”
She acknowledged certain limitations of the study, including that differences in the degree of underreporting on death certificates across racial groups could bias the results. “The Eight Americas framework does not allow for evaluation of ethnicity,” she added. “We were also unable to examine causes for the disparities in SLE mortality. One could argue that there are a lot of other social factors that are likely race related that are not necessarily captured by the Eight Americas. Also, as with most epidemiological studies, we cannot rule out the role that ecological fallacy may play where the population average may not be appropriate in estimating an individual’s risk of mortality.”
One of the study coauthors reported receiving partial salary support through the Dr. Elaine Lambert Lupus Foundation via the John and Marcia Goldman Foundation and previously receiving salary support through a lupus-related grant from the Genomics Institute of the Novartis Research Foundation. The other coauthors reported having no relevant disclosures.
[email protected]
SAN DIEGO – Blacks with systemic lupus erythematosus (SLE) who share the same social and geographic contexts as whites with the disease were disproportionately more likely to die young and to show severe patterns of mortality, according to a study of death certificate data.
“One of the most salient aspects of the epidemiology of lupus is the predilection of the disease for women and racial minorities,” lead study author Titilola Falasinnu, PhD, said at the annual meeting of the American College of Rheumatology.
Dr. Falasinnu, a postdoctoral fellow in Stanford (Calif.) University’s department of health research and policy, and her associates examined SLE mortality across eight groups of race-county combinations published in 2006 and known as the “Eight Americas” (PLoS Med. 2006 Sep 12;3[9]:e260). This seminal work, which has been validated across multiple disease states, jointly characterized race, socioeconomic status, and geographical location in relation to health disparities in the United States to demonstrate the most important factors accounting for these disparities within the Eight Americas.
For the current analysis, Dr. Falasinnu and her associates were most interested in America 6 (black middle America), America 7 (Southern low-income rural blacks), and America 8 (high-risk urban blacks). “The question we wanted to ask is whether, on average, poorer individuals have more severe SLE mortality experiences, compared with richer individuals in the black community,” she said. “What happens when you hold race constant and you vary socioeconomic indices?” Using death certificate data from the National Center for Health Statistics Multiple Causes of Death database, they identified SLE-related deaths between 2003 and 2014. Next, they compared these data with mortality statistics from each of the Eight Americas.
In all, there were nearly 25,000 SLE-related deaths, of which 85% were female. More than one-third of deaths occurred among those aged 45-64 years, and the mean age at death was 57 years. More than half of deaths (64%) occurred among whites, and 31% among blacks. Among SLE decedents, northern rural whites in America 2 had the lowest mortality rates. Blacks in America 6, 7, and 8 had the highest mortality, yet there were no significant differences in the death rates among those three groups. “We found that in general, blacks were three times more likely to die with SLE, compared with those in America 3 [middle America],” Dr. Falasinnu said.
Asians, Native Americans, and blacks with SLE died at an average age of 48-49 years, regardless of their social context, while Northern whites had the highest life expectancy: an average age of 69 years. They also found that 17% of SLE deaths in America 2 occurred before the age of 50 years, compared with more than 50% in Americas 6, 7, and 8. The most frequently reported associated causes of death were cardiovascular disease (about 50% of all SLE-related deaths) and kidney manifestations (about 20% of all SLE-related deaths). Compared with those in America 3, racial minorities had a 23%-53% higher risk of infections, a 5%-64% higher risk of kidney disease, a 7%-23% lower risk of cardiovascular disease, and a 20%-52% lower risk of cancers.
“Although blacks inhabited three vastly different geographical and social contexts, SLE mortality parameters did not vary among socially advantaged and disadvantaged black Americas,” Dr. Falasinnu concluded. “Blacks sharing the same social and geographical contexts as whites were disproportionately more likely to die young and exhibit patterns of mortality associated with active SLE disease.”
She acknowledged certain limitations of the study, including that differences in the degree of underreporting on death certificates across racial groups could bias the results. “The Eight Americas framework does not allow for evaluation of ethnicity,” she added. “We were also unable to examine causes for the disparities in SLE mortality. One could argue that there are a lot of other social factors that are likely race related that are not necessarily captured by the Eight Americas. Also, as with most epidemiological studies, we cannot rule out the role that ecological fallacy may play where the population average may not be appropriate in estimating an individual’s risk of mortality.”
One of the study coauthors reported receiving partial salary support through the Dr. Elaine Lambert Lupus Foundation via the John and Marcia Goldman Foundation and previously receiving salary support through a lupus-related grant from the Genomics Institute of the Novartis Research Foundation. The other coauthors reported having no relevant disclosures.
[email protected]
AT ACR 2017
Key clinical point: Blacks sharing the same social and geographical contexts as whites were more likely to die young and exhibit patterns of mortality associated with active SLE disease.
Major finding: Blacks in three race-geographic contexts were about three times more likely than whites in middle America to die with SLE.
Study details: An analysis of nearly 25,000 SLE-related deaths from the National Center for Health Statistics Multiple Causes of Death database.
Disclosures: One of the study coauthors reported receiving partial salary support through the Dr. Elaine Lambert Lupus Foundation via the John and Marcia Goldman Foundation and previously receiving salary support through a lupus-related grant from the Genomics Institute of the Novartis Research Foundation. The other coauthors reported having no relevant disclosures.
Mutations influence prognostic value of tumor location in stage III colon cancer
Among patients with resected stage III colon cancer, the prognostic value of primary tumor location varied according to patients’ BRAF or RAS mutational status, according to a post hoc analysis of patients in the Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 trial.
Specifically, in patients with BRAF or RAS mutations, disease-free survival (DFS) was better in right-sided vs. left-sided tumors, while in patients with RAS and BRAF double wild type, DFS was worse in right-sided vs. left-sided tumors, authors of the study reported in JAMA Oncology.
Right-sided tumor location has been associated with poor survival in previous studies of patients with metastatic colorectal cancer. However, for patients with stage III disease, such as those in this study, little is known about how tumor sidedness affects outcomes, the investigators wrote (JAMA Oncol. 2017 Nov 22. doi: 10.1001/jamaoncol.2017.3695).
“Although primary tumor location does not seem to be associated with DFS in the whole study population, opposite sidedness prognostic values are observed for RAS and BRAF wild-type and mutant tumors,” wrote Julien Taieb, MD, PhD, Department of Hepatogastroenterology and GI Oncology, Hôpital Européen Georges-Pompidou, Paris, and his coauthors.
The post hoc analysis included 1,869 resected stage III colon cancer patients with full information on primary tumor location in the PETACC-8 phase 3 randomized trial. The primary objective of the trial was to evaluate adjuvant treatment with the FOLFOX regimen with or without cetuximab.
Forty percent of the patients had a right-sided tumor, data show.
Right-sided tumor location was not prognostic for DFS for all patients, though it was associated with shorter survival after relapse (hazard ratio, 1.54; 95% confidence interval, 1.23-1.93; P = .001) and overall survival (HR, 1.25; 95%CI, 1.02-1.54; P = .03).
However, when looking at different molecular subgroups, Dr. Taieb and his colleagues found that DFS was better in right-sided vs. left-sided tumors in patients with RAS mutations (HR, 0.80; 95% CI, 0.64-1.00; P = .046), and similar findings were seen in BRAF-mutated tumors.
Conversely, DFS was worse in right-sided vs. left-sided tumors among those patients with RAS and BRAF double wild type (HR, 1.39; 95% CI, 1.01-1.92; P = .04), the investigators reported.
Investigators also sought to evaluate whether tumor location predicted the benefit of cetuximab.
However, “no benefit of adding cetuximab to FOLFOX was observed in our population of patients with stage III left-sided tumors, nor was any detrimental effect of adding cetuximab observed in right-sided tumors,” Dr. Taieb and his coauthors wrote.
PETACC-8 was sponsored by the Fédération Francophone de Cancérologie Digestive with some support from Merck KGaA and Sanofi-Aventis. Dr. Taieb reported participating in consulting or advisory boards for Merck KGaA, Sanofi, Roche/Genentech, Pfizer, and Amgen.
Among patients with resected stage III colon cancer, the prognostic value of primary tumor location varied according to patients’ BRAF or RAS mutational status, according to a post hoc analysis of patients in the Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 trial.
Specifically, in patients with BRAF or RAS mutations, disease-free survival (DFS) was better in right-sided vs. left-sided tumors, while in patients with RAS and BRAF double wild type, DFS was worse in right-sided vs. left-sided tumors, authors of the study reported in JAMA Oncology.
Right-sided tumor location has been associated with poor survival in previous studies of patients with metastatic colorectal cancer. However, for patients with stage III disease, such as those in this study, little is known about how tumor sidedness affects outcomes, the investigators wrote (JAMA Oncol. 2017 Nov 22. doi: 10.1001/jamaoncol.2017.3695).
“Although primary tumor location does not seem to be associated with DFS in the whole study population, opposite sidedness prognostic values are observed for RAS and BRAF wild-type and mutant tumors,” wrote Julien Taieb, MD, PhD, Department of Hepatogastroenterology and GI Oncology, Hôpital Européen Georges-Pompidou, Paris, and his coauthors.
The post hoc analysis included 1,869 resected stage III colon cancer patients with full information on primary tumor location in the PETACC-8 phase 3 randomized trial. The primary objective of the trial was to evaluate adjuvant treatment with the FOLFOX regimen with or without cetuximab.
Forty percent of the patients had a right-sided tumor, data show.
Right-sided tumor location was not prognostic for DFS for all patients, though it was associated with shorter survival after relapse (hazard ratio, 1.54; 95% confidence interval, 1.23-1.93; P = .001) and overall survival (HR, 1.25; 95%CI, 1.02-1.54; P = .03).
However, when looking at different molecular subgroups, Dr. Taieb and his colleagues found that DFS was better in right-sided vs. left-sided tumors in patients with RAS mutations (HR, 0.80; 95% CI, 0.64-1.00; P = .046), and similar findings were seen in BRAF-mutated tumors.
Conversely, DFS was worse in right-sided vs. left-sided tumors among those patients with RAS and BRAF double wild type (HR, 1.39; 95% CI, 1.01-1.92; P = .04), the investigators reported.
Investigators also sought to evaluate whether tumor location predicted the benefit of cetuximab.
However, “no benefit of adding cetuximab to FOLFOX was observed in our population of patients with stage III left-sided tumors, nor was any detrimental effect of adding cetuximab observed in right-sided tumors,” Dr. Taieb and his coauthors wrote.
PETACC-8 was sponsored by the Fédération Francophone de Cancérologie Digestive with some support from Merck KGaA and Sanofi-Aventis. Dr. Taieb reported participating in consulting or advisory boards for Merck KGaA, Sanofi, Roche/Genentech, Pfizer, and Amgen.
Among patients with resected stage III colon cancer, the prognostic value of primary tumor location varied according to patients’ BRAF or RAS mutational status, according to a post hoc analysis of patients in the Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 trial.
Specifically, in patients with BRAF or RAS mutations, disease-free survival (DFS) was better in right-sided vs. left-sided tumors, while in patients with RAS and BRAF double wild type, DFS was worse in right-sided vs. left-sided tumors, authors of the study reported in JAMA Oncology.
Right-sided tumor location has been associated with poor survival in previous studies of patients with metastatic colorectal cancer. However, for patients with stage III disease, such as those in this study, little is known about how tumor sidedness affects outcomes, the investigators wrote (JAMA Oncol. 2017 Nov 22. doi: 10.1001/jamaoncol.2017.3695).
“Although primary tumor location does not seem to be associated with DFS in the whole study population, opposite sidedness prognostic values are observed for RAS and BRAF wild-type and mutant tumors,” wrote Julien Taieb, MD, PhD, Department of Hepatogastroenterology and GI Oncology, Hôpital Européen Georges-Pompidou, Paris, and his coauthors.
The post hoc analysis included 1,869 resected stage III colon cancer patients with full information on primary tumor location in the PETACC-8 phase 3 randomized trial. The primary objective of the trial was to evaluate adjuvant treatment with the FOLFOX regimen with or without cetuximab.
Forty percent of the patients had a right-sided tumor, data show.
Right-sided tumor location was not prognostic for DFS for all patients, though it was associated with shorter survival after relapse (hazard ratio, 1.54; 95% confidence interval, 1.23-1.93; P = .001) and overall survival (HR, 1.25; 95%CI, 1.02-1.54; P = .03).
However, when looking at different molecular subgroups, Dr. Taieb and his colleagues found that DFS was better in right-sided vs. left-sided tumors in patients with RAS mutations (HR, 0.80; 95% CI, 0.64-1.00; P = .046), and similar findings were seen in BRAF-mutated tumors.
Conversely, DFS was worse in right-sided vs. left-sided tumors among those patients with RAS and BRAF double wild type (HR, 1.39; 95% CI, 1.01-1.92; P = .04), the investigators reported.
Investigators also sought to evaluate whether tumor location predicted the benefit of cetuximab.
However, “no benefit of adding cetuximab to FOLFOX was observed in our population of patients with stage III left-sided tumors, nor was any detrimental effect of adding cetuximab observed in right-sided tumors,” Dr. Taieb and his coauthors wrote.
PETACC-8 was sponsored by the Fédération Francophone de Cancérologie Digestive with some support from Merck KGaA and Sanofi-Aventis. Dr. Taieb reported participating in consulting or advisory boards for Merck KGaA, Sanofi, Roche/Genentech, Pfizer, and Amgen.
FROM JAMA ONCOLOGY
Key clinical point: In patients with resected stage III colon cancer, prognosis associated with right-sided vs. left-sided tumors appears to vary according to RAS and BRAF mutational status.
Major finding: In patients with RAS mutations, DFS was better in right-sided vs. left-sided tumors (HR, 0.80; 95% CI, 0.64-1.00; P = .046), while in patients with RAS and BRAF double wild type, DFS was worse in right-sided vs. left-sided tumors (HR, 1.39; 95% CI, 1.01-1.92; P = .04).
Data source: A post hoc analysis of 1,869 patients in the Pan-European Trials in Alimentary Tract Cancer (PETACC)-8 phase 3 randomized trial with available tumor blocks of resected stage III colon adenocarcinoma.
Disclosures: PETACC-8 was sponsored by the Fédération Francophone de Cancérologie Digestive with some support from Merck KGaA and Sanofi-Aventis. Study authors reported various disclosures; first author Julien Taieb, MD, PhD reported participating in consulting or advisory boards for Merck KGaA, Sanofi, Roche/Genentech, Pfizer, and Amgen.
Does incretin therapy increase pancreatic cancer risk?
Risk of pancreatic cancer doubled among diabetes patients on incretin therapy in a recent retrospective cohort study, although it is unlikely that the drugs actually caused the increase, according to investigators.
, wrote Dr. Mathieu Boniol, vice president of statistics, International Prevention Research Institute, Lyon, France, and colleagues.
The study was sparked by concerns about a possible increased risk of cancer among patients prescribed incretin drugs, which include glucagonlike peptide receptor–1 (GLP-1R) agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors, authors said.
Results of the retrospective cohort analysis are based on two European public health insurance databases, comprising 33,292 diabetes patients treated with incretin drugs and 525,733 treated with other noninsulin antidiabetic drugs.
The risk of pancreatic cancer doubled for patients receiving incretin treatment (adjusted hazard ratio, 2.14; 95% confidence interval, 1.71-2.67), compared with patients receiving other noninsulin drugs, after adjusting for age, sex, and whether or not patients subsequently received an insulin prescription, investigators reported.
However, risk of pancreatic cancer decreased over time in patients on incretin therapy, according to further analyses by Dr. Boniol and colleagues.
That finding of diminishing risk over time argues against concluding that incretin drugs cause pancreatic cancer, according to investigators.
“A direct causal effect could be suspected if a steadily increasing risk of pancreatic cancer was associated with a steadily longer exposure to incretin drugs,” they said.
In the first 3 months after the first incretin prescription, risk of pancreatic cancer was 3.35 times greater (95% CI, 2.32-4.84), which “gradually diminished” to 1.69 (95% CI, 1.12-2.55) a year after the first prescription, the investigators said in the report.
As such, these new data do not help prove or disprove a causal link between incretin use and pancreatic cancer, continued Dr. Hellman, a past president of the American Association of Clinical Endocrinologists.
“I think, right now, we don’t have the data,” he said in an interview. “It’s a question that makes us nervous, because of what we know about the laboratory effects of the drugs, but we don’t have the answer yet. We need longer studies with larger numbers of people to answer that question.”
The study, funded by Sanofi, was conducted at the request of the European Medicines Agency to assess risk of pancreatic cancer associated with lixisenatide. However, the study covers a period prior to use of lixisenatide in the general population because the approval of the GLP-1R agonist was “too recent,” the study authors wrote.
The analyses in the study were conducted in 2015 and 2016 for two cohorts of subjects: one in Belgium, for which data had been collected from 2008 to 2013, and one in Italy, with data from 2000 to 2012.
Further studies are needed to assess how long-term use of incretin drugs may affect risk of pancreatic cancer, the authors said.
The analysis was conducted as part of a postauthorization safety study requested by the European Medicines Agency and funded by Sanofi. One study author reported receiving grants from Roche, Amgen, and Bristol-Myers Squibb outside the submitted work; the remaining investigators had no relevant financial disclosures.
Risk of pancreatic cancer doubled among diabetes patients on incretin therapy in a recent retrospective cohort study, although it is unlikely that the drugs actually caused the increase, according to investigators.
, wrote Dr. Mathieu Boniol, vice president of statistics, International Prevention Research Institute, Lyon, France, and colleagues.
The study was sparked by concerns about a possible increased risk of cancer among patients prescribed incretin drugs, which include glucagonlike peptide receptor–1 (GLP-1R) agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors, authors said.
Results of the retrospective cohort analysis are based on two European public health insurance databases, comprising 33,292 diabetes patients treated with incretin drugs and 525,733 treated with other noninsulin antidiabetic drugs.
The risk of pancreatic cancer doubled for patients receiving incretin treatment (adjusted hazard ratio, 2.14; 95% confidence interval, 1.71-2.67), compared with patients receiving other noninsulin drugs, after adjusting for age, sex, and whether or not patients subsequently received an insulin prescription, investigators reported.
However, risk of pancreatic cancer decreased over time in patients on incretin therapy, according to further analyses by Dr. Boniol and colleagues.
That finding of diminishing risk over time argues against concluding that incretin drugs cause pancreatic cancer, according to investigators.
“A direct causal effect could be suspected if a steadily increasing risk of pancreatic cancer was associated with a steadily longer exposure to incretin drugs,” they said.
In the first 3 months after the first incretin prescription, risk of pancreatic cancer was 3.35 times greater (95% CI, 2.32-4.84), which “gradually diminished” to 1.69 (95% CI, 1.12-2.55) a year after the first prescription, the investigators said in the report.
As such, these new data do not help prove or disprove a causal link between incretin use and pancreatic cancer, continued Dr. Hellman, a past president of the American Association of Clinical Endocrinologists.
“I think, right now, we don’t have the data,” he said in an interview. “It’s a question that makes us nervous, because of what we know about the laboratory effects of the drugs, but we don’t have the answer yet. We need longer studies with larger numbers of people to answer that question.”
The study, funded by Sanofi, was conducted at the request of the European Medicines Agency to assess risk of pancreatic cancer associated with lixisenatide. However, the study covers a period prior to use of lixisenatide in the general population because the approval of the GLP-1R agonist was “too recent,” the study authors wrote.
The analyses in the study were conducted in 2015 and 2016 for two cohorts of subjects: one in Belgium, for which data had been collected from 2008 to 2013, and one in Italy, with data from 2000 to 2012.
Further studies are needed to assess how long-term use of incretin drugs may affect risk of pancreatic cancer, the authors said.
The analysis was conducted as part of a postauthorization safety study requested by the European Medicines Agency and funded by Sanofi. One study author reported receiving grants from Roche, Amgen, and Bristol-Myers Squibb outside the submitted work; the remaining investigators had no relevant financial disclosures.
Risk of pancreatic cancer doubled among diabetes patients on incretin therapy in a recent retrospective cohort study, although it is unlikely that the drugs actually caused the increase, according to investigators.
, wrote Dr. Mathieu Boniol, vice president of statistics, International Prevention Research Institute, Lyon, France, and colleagues.
The study was sparked by concerns about a possible increased risk of cancer among patients prescribed incretin drugs, which include glucagonlike peptide receptor–1 (GLP-1R) agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors, authors said.
Results of the retrospective cohort analysis are based on two European public health insurance databases, comprising 33,292 diabetes patients treated with incretin drugs and 525,733 treated with other noninsulin antidiabetic drugs.
The risk of pancreatic cancer doubled for patients receiving incretin treatment (adjusted hazard ratio, 2.14; 95% confidence interval, 1.71-2.67), compared with patients receiving other noninsulin drugs, after adjusting for age, sex, and whether or not patients subsequently received an insulin prescription, investigators reported.
However, risk of pancreatic cancer decreased over time in patients on incretin therapy, according to further analyses by Dr. Boniol and colleagues.
That finding of diminishing risk over time argues against concluding that incretin drugs cause pancreatic cancer, according to investigators.
“A direct causal effect could be suspected if a steadily increasing risk of pancreatic cancer was associated with a steadily longer exposure to incretin drugs,” they said.
In the first 3 months after the first incretin prescription, risk of pancreatic cancer was 3.35 times greater (95% CI, 2.32-4.84), which “gradually diminished” to 1.69 (95% CI, 1.12-2.55) a year after the first prescription, the investigators said in the report.
As such, these new data do not help prove or disprove a causal link between incretin use and pancreatic cancer, continued Dr. Hellman, a past president of the American Association of Clinical Endocrinologists.
“I think, right now, we don’t have the data,” he said in an interview. “It’s a question that makes us nervous, because of what we know about the laboratory effects of the drugs, but we don’t have the answer yet. We need longer studies with larger numbers of people to answer that question.”
The study, funded by Sanofi, was conducted at the request of the European Medicines Agency to assess risk of pancreatic cancer associated with lixisenatide. However, the study covers a period prior to use of lixisenatide in the general population because the approval of the GLP-1R agonist was “too recent,” the study authors wrote.
The analyses in the study were conducted in 2015 and 2016 for two cohorts of subjects: one in Belgium, for which data had been collected from 2008 to 2013, and one in Italy, with data from 2000 to 2012.
Further studies are needed to assess how long-term use of incretin drugs may affect risk of pancreatic cancer, the authors said.
The analysis was conducted as part of a postauthorization safety study requested by the European Medicines Agency and funded by Sanofi. One study author reported receiving grants from Roche, Amgen, and Bristol-Myers Squibb outside the submitted work; the remaining investigators had no relevant financial disclosures.
FROM DIABETES CARE
Key clinical point: Incretin therapy was associated with increased pancreatic cancer risk, but possibly because of occult pancreatic cancer that aggravates diabetes.
Major finding: Patients receiving incretin drugs had a doubling of pancreatic cancer risk (aHR 2.14 (95% CI, 1.71-2.67).
Data source: Retrospective cohort analysis of public health insurance databases including 33,292 diabetes patients treated with incretin drugs and 525,733 treated with another noninsulin antidiabetic drug.
Disclosures: The analysis was conducted as part of a postauthorization safety study requested by the European Medicines Agency and funded by Sanofi. One study author reported receiving grants from Roche, Amgen, and Bristol-Myers Squibb outside the submitted work; the remaining investigators had no relevant financial disclosures.
Consider calcipotriol contact allergy when psoriasis doesn’t improve
Researchers at the University of Leuven (Belgium) conducted patch tests on six patients between 2004 and 2016 who presented with psoriasis that did not improve with use of topical calcipotriol.
Reports of contact allergy to calcipotriol are rare in the literature, considering its widespread use. However, the patch testing and successful alternative treatment confirmed the diagnosis of allergic contact dermatitis in all six cases.
“The lesions improved following replacement of calcipotriol therapy with topical corticosteroids and/or oral medication,” wrote An Goossens, MD, of the contact allergy unit in the department of dermatology at the university.
Five of the patients were adults ranging in age from 26 to 59 years (two men and three women), and the sixth was a 10-year-old girl. They all had lesions on their feet, scalp, or hands.
The successful patch test consisted of a 2 mcg/mL solution of calcipotriol in citrate-buffered isopropanol.
Patients who are diagnosed with this specific allergy may be able to tolerate treatment with a different topical vitamin D analog such as tacalcitol (Contact Derm. 2017 Nov. doi: 10.1111/cod.12910).
Researchers at the University of Leuven (Belgium) conducted patch tests on six patients between 2004 and 2016 who presented with psoriasis that did not improve with use of topical calcipotriol.
Reports of contact allergy to calcipotriol are rare in the literature, considering its widespread use. However, the patch testing and successful alternative treatment confirmed the diagnosis of allergic contact dermatitis in all six cases.
“The lesions improved following replacement of calcipotriol therapy with topical corticosteroids and/or oral medication,” wrote An Goossens, MD, of the contact allergy unit in the department of dermatology at the university.
Five of the patients were adults ranging in age from 26 to 59 years (two men and three women), and the sixth was a 10-year-old girl. They all had lesions on their feet, scalp, or hands.
The successful patch test consisted of a 2 mcg/mL solution of calcipotriol in citrate-buffered isopropanol.
Patients who are diagnosed with this specific allergy may be able to tolerate treatment with a different topical vitamin D analog such as tacalcitol (Contact Derm. 2017 Nov. doi: 10.1111/cod.12910).
Researchers at the University of Leuven (Belgium) conducted patch tests on six patients between 2004 and 2016 who presented with psoriasis that did not improve with use of topical calcipotriol.
Reports of contact allergy to calcipotriol are rare in the literature, considering its widespread use. However, the patch testing and successful alternative treatment confirmed the diagnosis of allergic contact dermatitis in all six cases.
“The lesions improved following replacement of calcipotriol therapy with topical corticosteroids and/or oral medication,” wrote An Goossens, MD, of the contact allergy unit in the department of dermatology at the university.
Five of the patients were adults ranging in age from 26 to 59 years (two men and three women), and the sixth was a 10-year-old girl. They all had lesions on their feet, scalp, or hands.
The successful patch test consisted of a 2 mcg/mL solution of calcipotriol in citrate-buffered isopropanol.
Patients who are diagnosed with this specific allergy may be able to tolerate treatment with a different topical vitamin D analog such as tacalcitol (Contact Derm. 2017 Nov. doi: 10.1111/cod.12910).
FROM CONTACT DERMATITIS
Tezacaftor-ivacaftor combo shows promise in cystic fibrosis
A new drug that targets the cystic fibrosis transmembrane conductance regulator protein could significantly improve lung function and other symptoms in patients with cystic fibrosis.
In a phase 3 double-blind, placebo controlled crossover trial, researchers examined the effects of tezacaftor – a cystic fibrosis transmembrane conductance regulator (CFTR) corrector – in combination with the CFTR potentiator ivacaftor, compared with ivacaftor alone or placebo.
“The addition of the CFTR corrector tezacaftor was hypothesized to enhance clinical benefit in patients with these mutations by increasing overall CFTR function,” wrote Dr. Steven M. Rowe of the division of pulmonary, allergy, and critical care medicine at the University of Alabama at Birmingham, and his coauthors. “This combination treatment is particularly important for restoring activity to those carrying two copies of the Phe508del CFTR mutation, as shown for the approved corrector-potentiator combination lumacaftor-ivacaftor, and may provide benefit to patients with other CFTR mutations.”
After two 8-week treatment periods in which patients were randomized to two of the three regimens, separated by an 8-week washout period, researchers saw significant improvements in predicted forced expiratory volume in 1 second (FEV1), both with tezacaftor-ivacaftor and ivacaftor alone, compared with placebo (N Engl J Med. 2017 Nov 23;377:2024-35. doi: 10.1056/NEJMoa1709847).
From baseline to the average of week 4 and 8, the combination of tezacaftor-ivacaftor was associated with a 6.8-percentage-point absolute change, and there was a 4.7-percentage-point improvement with ivacaftor alone compared with placebo. The difference between the tezacaftor-ivacaftor combination and ivacaftor monotherapy was also statistically significant in favor of the combination treatment.
Researchers also saw significant improvements in the secondary endpoint of absolute change in the Cystic Fibrosis Questionnaire–Revised score; the combination treatment was associated with an 11.1 point improvement compared with placebo, and monotherapy achieved a 9.7-point improvement. In the combination therapy group, 65% of patients achieved a clinically important difference of 4 points or greater, compared with 58% of patients in the monotherapy group and 33% of patients in the placebo group.
“These findings confirm the benefits of potentiator therapy in patients with residual CFTR function mutations and the added benefit conferred by corrector-potentiator combination therapy in this population,” the authors wrote.
The investigators also saw a lower rate of pulmonary exacerbations in the combined therapy group, but this did not reach statistical significance.
The rate of adverse events was similar across all three groups. Most were considered mild or moderate in severity and were largely clinical manifestations of cystic fibrosis.
Vertex Pharmaceuticals, which manufactures tezacaftor and ivacaftor, funded the study. Twelve of the thirteen authors reported receiving various kinds of support from Vertex, including personal fees, grant support, and nonfinancial support. Several authors reported ties to other industry sources.
This NEJM article came out with a companion article reporting phase 3 tezacaftor-ivacaftor results in homozygous CFTR Phe508del patients. Tezacaftor is a CFTR corrector developed by a company that has another corrector on the market, called lumacaftor. Lumacaftor is formulated with ivacaftor and available in the United States for patients age 6 and above who have two copies of Phe508del. It is exciting that another combination therapy has been developed that appears to be very effective and can be used for a second group of patients. This era of personalized medicine is extremely exciting, and we look forward to future therapies for all CFTR mutations.
This NEJM article came out with a companion article reporting phase 3 tezacaftor-ivacaftor results in homozygous CFTR Phe508del patients. Tezacaftor is a CFTR corrector developed by a company that has another corrector on the market, called lumacaftor. Lumacaftor is formulated with ivacaftor and available in the United States for patients age 6 and above who have two copies of Phe508del. It is exciting that another combination therapy has been developed that appears to be very effective and can be used for a second group of patients. This era of personalized medicine is extremely exciting, and we look forward to future therapies for all CFTR mutations.
This NEJM article came out with a companion article reporting phase 3 tezacaftor-ivacaftor results in homozygous CFTR Phe508del patients. Tezacaftor is a CFTR corrector developed by a company that has another corrector on the market, called lumacaftor. Lumacaftor is formulated with ivacaftor and available in the United States for patients age 6 and above who have two copies of Phe508del. It is exciting that another combination therapy has been developed that appears to be very effective and can be used for a second group of patients. This era of personalized medicine is extremely exciting, and we look forward to future therapies for all CFTR mutations.
A new drug that targets the cystic fibrosis transmembrane conductance regulator protein could significantly improve lung function and other symptoms in patients with cystic fibrosis.
In a phase 3 double-blind, placebo controlled crossover trial, researchers examined the effects of tezacaftor – a cystic fibrosis transmembrane conductance regulator (CFTR) corrector – in combination with the CFTR potentiator ivacaftor, compared with ivacaftor alone or placebo.
“The addition of the CFTR corrector tezacaftor was hypothesized to enhance clinical benefit in patients with these mutations by increasing overall CFTR function,” wrote Dr. Steven M. Rowe of the division of pulmonary, allergy, and critical care medicine at the University of Alabama at Birmingham, and his coauthors. “This combination treatment is particularly important for restoring activity to those carrying two copies of the Phe508del CFTR mutation, as shown for the approved corrector-potentiator combination lumacaftor-ivacaftor, and may provide benefit to patients with other CFTR mutations.”
After two 8-week treatment periods in which patients were randomized to two of the three regimens, separated by an 8-week washout period, researchers saw significant improvements in predicted forced expiratory volume in 1 second (FEV1), both with tezacaftor-ivacaftor and ivacaftor alone, compared with placebo (N Engl J Med. 2017 Nov 23;377:2024-35. doi: 10.1056/NEJMoa1709847).
From baseline to the average of week 4 and 8, the combination of tezacaftor-ivacaftor was associated with a 6.8-percentage-point absolute change, and there was a 4.7-percentage-point improvement with ivacaftor alone compared with placebo. The difference between the tezacaftor-ivacaftor combination and ivacaftor monotherapy was also statistically significant in favor of the combination treatment.
Researchers also saw significant improvements in the secondary endpoint of absolute change in the Cystic Fibrosis Questionnaire–Revised score; the combination treatment was associated with an 11.1 point improvement compared with placebo, and monotherapy achieved a 9.7-point improvement. In the combination therapy group, 65% of patients achieved a clinically important difference of 4 points or greater, compared with 58% of patients in the monotherapy group and 33% of patients in the placebo group.
“These findings confirm the benefits of potentiator therapy in patients with residual CFTR function mutations and the added benefit conferred by corrector-potentiator combination therapy in this population,” the authors wrote.
The investigators also saw a lower rate of pulmonary exacerbations in the combined therapy group, but this did not reach statistical significance.
The rate of adverse events was similar across all three groups. Most were considered mild or moderate in severity and were largely clinical manifestations of cystic fibrosis.
Vertex Pharmaceuticals, which manufactures tezacaftor and ivacaftor, funded the study. Twelve of the thirteen authors reported receiving various kinds of support from Vertex, including personal fees, grant support, and nonfinancial support. Several authors reported ties to other industry sources.
A new drug that targets the cystic fibrosis transmembrane conductance regulator protein could significantly improve lung function and other symptoms in patients with cystic fibrosis.
In a phase 3 double-blind, placebo controlled crossover trial, researchers examined the effects of tezacaftor – a cystic fibrosis transmembrane conductance regulator (CFTR) corrector – in combination with the CFTR potentiator ivacaftor, compared with ivacaftor alone or placebo.
“The addition of the CFTR corrector tezacaftor was hypothesized to enhance clinical benefit in patients with these mutations by increasing overall CFTR function,” wrote Dr. Steven M. Rowe of the division of pulmonary, allergy, and critical care medicine at the University of Alabama at Birmingham, and his coauthors. “This combination treatment is particularly important for restoring activity to those carrying two copies of the Phe508del CFTR mutation, as shown for the approved corrector-potentiator combination lumacaftor-ivacaftor, and may provide benefit to patients with other CFTR mutations.”
After two 8-week treatment periods in which patients were randomized to two of the three regimens, separated by an 8-week washout period, researchers saw significant improvements in predicted forced expiratory volume in 1 second (FEV1), both with tezacaftor-ivacaftor and ivacaftor alone, compared with placebo (N Engl J Med. 2017 Nov 23;377:2024-35. doi: 10.1056/NEJMoa1709847).
From baseline to the average of week 4 and 8, the combination of tezacaftor-ivacaftor was associated with a 6.8-percentage-point absolute change, and there was a 4.7-percentage-point improvement with ivacaftor alone compared with placebo. The difference between the tezacaftor-ivacaftor combination and ivacaftor monotherapy was also statistically significant in favor of the combination treatment.
Researchers also saw significant improvements in the secondary endpoint of absolute change in the Cystic Fibrosis Questionnaire–Revised score; the combination treatment was associated with an 11.1 point improvement compared with placebo, and monotherapy achieved a 9.7-point improvement. In the combination therapy group, 65% of patients achieved a clinically important difference of 4 points or greater, compared with 58% of patients in the monotherapy group and 33% of patients in the placebo group.
“These findings confirm the benefits of potentiator therapy in patients with residual CFTR function mutations and the added benefit conferred by corrector-potentiator combination therapy in this population,” the authors wrote.
The investigators also saw a lower rate of pulmonary exacerbations in the combined therapy group, but this did not reach statistical significance.
The rate of adverse events was similar across all three groups. Most were considered mild or moderate in severity and were largely clinical manifestations of cystic fibrosis.
Vertex Pharmaceuticals, which manufactures tezacaftor and ivacaftor, funded the study. Twelve of the thirteen authors reported receiving various kinds of support from Vertex, including personal fees, grant support, and nonfinancial support. Several authors reported ties to other industry sources.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: The combination of tezacaftor and ivacaftor is associated with significant improvements in lung function in cystic fibrosis, compared with placebo or ivacaftor alone.
Major finding: Combined treatment with tezacaftor-ivacaftor was associated with a 6.8-percentage-point absolute change in FEV1 compared with placebo.
Data source: A phase 3 double-blind, placebo controlled, randomized crossover trial of 248 patients with cystic fibrosis.
Disclosures: Vertex Pharmaceuticals, which manufactures tezacaftor and ivacaftor, funded the study. Twelve of the thirteen authors reported receiving various kinds of support from Vertex, including personal fees, grant support, and nonfinancial support. Several authors reported ties to other industry sources.
Preventing substance use
Substance use disorders are affecting every pediatric practice as they are major contributors to morbidity and mortality in young people. With the ongoing risks of binge drinking, the current epidemic of opioid addiction and overdose deaths in the United States, and the shifting legal status and public perception of the risk of marijuana, how to deal with substance use disorders seems to be the focus of public conversation these days. , such as parent education and early recognition in pediatric practice.
Substance abuse risk
We cannot yet predict who can safely “experiment” with substances or who will develop dependency. However, there is information that we can use to identify those at greater risk. Youth who have a first-degree relative with a substance use disorder are at greater risk for developing such a disorder themselves, and this is especially so if there is a family history of alcoholism. Youth who suffer from a psychiatric illness, particularly from anxiety and mood disorders, have a special vulnerability to abusing substances, particularly when their underlying illness is untreated or incompletely treated. Youth with ADHD are at substantially elevated risk of developing substance use disorders, although there is a complex relationship between these two problems. The evidence currently suggests that for youth who began effective treatment prior to puberty, there is no elevation in risk, but for those who did not, there is a substantially elevated risk of substance use disorders. Finally, there has been research that indicates that children with a combination of sensation-seeking, high impulsivity, anxiety-sensitivity, and hopelessness are at the highest risk for substance use disorders.2
Prevention efforts you can make: To your patients
The first step in your prevention efforts is an open conversation about drugs and alcohol. Ask your middle schoolers about whether they have tried alcohol or any drugs. Have their friends? What are kids saying about alcohol? About marijuana? Vaping? Are there other substances that kids are talking about or trying? Be genuinely curious, warm, and nonjudgmental. Find out what they think the risks of these substances may be. If appropriate, offer them some education about known risks of substances to the developing brain, to school or athletic performance, and so on. You can teach them about other trusted resources, such as the National Institute on Drug Abuse (NIDA), which has a resource specifically for teens (teens.drugabuse.gov).
For your high school students and those heading off to college, provide a safe place to talk about what they have tried and whether they (or you) have any worries about substance use. You have a unique combination of clinical authority and expertise in them as individuals, and can help them meaningfully plan how to handle their choices. You might talk about the specific risks of binge drinking, from sexual assault to alcohol poisoning and permanent cognitive effects on their developing brains. They also can benefit from hearing about the actual risks of frequent marijuana use, including impaired cognitive performance (and permanent IQ decline), and ongoing risks to their still-developing brains. Don’t be surprised if your older adolescent patients want to educate you about risks. Be curious and humble, and don’t be afraid to go together to a third party for information. You should encourage their efforts to think critically, and be empathic to their dilemma as they try to balance risks against their drive to have new experiences, to be independent, and to be strongly connected to their peers.
Adolescents should hear about your concern about their specific risks with drugs and alcohol, such as a history of traumatic brain injury (concussion), a family history of drug or alcohol dependence, or their own diagnosis of anxiety, depression, or ADHD. You might point out that because they have not tried any drugs or alcohol in high school, they may be prone to having too much to drink when they first try it. Or you might observe that because they have an anxiety disorder, they are vulnerable to becoming dependent on alcohol. Hearing about their specific level of risk equips them to make wiser choices in the context of their growing autonomy.
Prevention efforts you can make: To the parents
Your other prevention strategies should include parents. Studies have shown that when parents have clear rules and expectations about drug and alcohol use, and are consistent about enforcing consequences in their home, their children are significantly less likely than their peers to have experimented with drugs or alcohol by their senior year in high school. Parents of children headed to middle school should hear about this fact, alongside accurate information about the risks associated with alcohol and specific drugs for the developing brain.
Finally, parents need to hear that they can be effective disciplinarians, while also making clear to their children that safety comes first, and that their rules should have clear exceptions for safety. If the parents have a rule against any use of alcohol or drugs, there should be an exception if their child is out and feels unsafe. If they are drunk, or their driver has been drinking, they can call for a ride and will not be in (much) trouble. Rules don’t have to be draconian to be effective; they should always support honesty and safety first. This is a lot of territory to cover, and you do not have to be the only resource for parents. Reliable online resources, such as NIDA’s and SAMHSA’s websites, are full of useful information, and others, such as teen-safe.org, have detailed resources for parents in particular.
References
1. Hum Genet. 2012 Jun;131(6):779-89.
2. Alcohol Clin Exp Res. 2013 Jan;37(Suppl 1):E281-90.
Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston.
Substance use disorders are affecting every pediatric practice as they are major contributors to morbidity and mortality in young people. With the ongoing risks of binge drinking, the current epidemic of opioid addiction and overdose deaths in the United States, and the shifting legal status and public perception of the risk of marijuana, how to deal with substance use disorders seems to be the focus of public conversation these days. , such as parent education and early recognition in pediatric practice.
Substance abuse risk
We cannot yet predict who can safely “experiment” with substances or who will develop dependency. However, there is information that we can use to identify those at greater risk. Youth who have a first-degree relative with a substance use disorder are at greater risk for developing such a disorder themselves, and this is especially so if there is a family history of alcoholism. Youth who suffer from a psychiatric illness, particularly from anxiety and mood disorders, have a special vulnerability to abusing substances, particularly when their underlying illness is untreated or incompletely treated. Youth with ADHD are at substantially elevated risk of developing substance use disorders, although there is a complex relationship between these two problems. The evidence currently suggests that for youth who began effective treatment prior to puberty, there is no elevation in risk, but for those who did not, there is a substantially elevated risk of substance use disorders. Finally, there has been research that indicates that children with a combination of sensation-seeking, high impulsivity, anxiety-sensitivity, and hopelessness are at the highest risk for substance use disorders.2
Prevention efforts you can make: To your patients
The first step in your prevention efforts is an open conversation about drugs and alcohol. Ask your middle schoolers about whether they have tried alcohol or any drugs. Have their friends? What are kids saying about alcohol? About marijuana? Vaping? Are there other substances that kids are talking about or trying? Be genuinely curious, warm, and nonjudgmental. Find out what they think the risks of these substances may be. If appropriate, offer them some education about known risks of substances to the developing brain, to school or athletic performance, and so on. You can teach them about other trusted resources, such as the National Institute on Drug Abuse (NIDA), which has a resource specifically for teens (teens.drugabuse.gov).
For your high school students and those heading off to college, provide a safe place to talk about what they have tried and whether they (or you) have any worries about substance use. You have a unique combination of clinical authority and expertise in them as individuals, and can help them meaningfully plan how to handle their choices. You might talk about the specific risks of binge drinking, from sexual assault to alcohol poisoning and permanent cognitive effects on their developing brains. They also can benefit from hearing about the actual risks of frequent marijuana use, including impaired cognitive performance (and permanent IQ decline), and ongoing risks to their still-developing brains. Don’t be surprised if your older adolescent patients want to educate you about risks. Be curious and humble, and don’t be afraid to go together to a third party for information. You should encourage their efforts to think critically, and be empathic to their dilemma as they try to balance risks against their drive to have new experiences, to be independent, and to be strongly connected to their peers.
Adolescents should hear about your concern about their specific risks with drugs and alcohol, such as a history of traumatic brain injury (concussion), a family history of drug or alcohol dependence, or their own diagnosis of anxiety, depression, or ADHD. You might point out that because they have not tried any drugs or alcohol in high school, they may be prone to having too much to drink when they first try it. Or you might observe that because they have an anxiety disorder, they are vulnerable to becoming dependent on alcohol. Hearing about their specific level of risk equips them to make wiser choices in the context of their growing autonomy.
Prevention efforts you can make: To the parents
Your other prevention strategies should include parents. Studies have shown that when parents have clear rules and expectations about drug and alcohol use, and are consistent about enforcing consequences in their home, their children are significantly less likely than their peers to have experimented with drugs or alcohol by their senior year in high school. Parents of children headed to middle school should hear about this fact, alongside accurate information about the risks associated with alcohol and specific drugs for the developing brain.
Finally, parents need to hear that they can be effective disciplinarians, while also making clear to their children that safety comes first, and that their rules should have clear exceptions for safety. If the parents have a rule against any use of alcohol or drugs, there should be an exception if their child is out and feels unsafe. If they are drunk, or their driver has been drinking, they can call for a ride and will not be in (much) trouble. Rules don’t have to be draconian to be effective; they should always support honesty and safety first. This is a lot of territory to cover, and you do not have to be the only resource for parents. Reliable online resources, such as NIDA’s and SAMHSA’s websites, are full of useful information, and others, such as teen-safe.org, have detailed resources for parents in particular.
References
1. Hum Genet. 2012 Jun;131(6):779-89.
2. Alcohol Clin Exp Res. 2013 Jan;37(Suppl 1):E281-90.
Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston.
Substance use disorders are affecting every pediatric practice as they are major contributors to morbidity and mortality in young people. With the ongoing risks of binge drinking, the current epidemic of opioid addiction and overdose deaths in the United States, and the shifting legal status and public perception of the risk of marijuana, how to deal with substance use disorders seems to be the focus of public conversation these days. , such as parent education and early recognition in pediatric practice.
Substance abuse risk
We cannot yet predict who can safely “experiment” with substances or who will develop dependency. However, there is information that we can use to identify those at greater risk. Youth who have a first-degree relative with a substance use disorder are at greater risk for developing such a disorder themselves, and this is especially so if there is a family history of alcoholism. Youth who suffer from a psychiatric illness, particularly from anxiety and mood disorders, have a special vulnerability to abusing substances, particularly when their underlying illness is untreated or incompletely treated. Youth with ADHD are at substantially elevated risk of developing substance use disorders, although there is a complex relationship between these two problems. The evidence currently suggests that for youth who began effective treatment prior to puberty, there is no elevation in risk, but for those who did not, there is a substantially elevated risk of substance use disorders. Finally, there has been research that indicates that children with a combination of sensation-seeking, high impulsivity, anxiety-sensitivity, and hopelessness are at the highest risk for substance use disorders.2
Prevention efforts you can make: To your patients
The first step in your prevention efforts is an open conversation about drugs and alcohol. Ask your middle schoolers about whether they have tried alcohol or any drugs. Have their friends? What are kids saying about alcohol? About marijuana? Vaping? Are there other substances that kids are talking about or trying? Be genuinely curious, warm, and nonjudgmental. Find out what they think the risks of these substances may be. If appropriate, offer them some education about known risks of substances to the developing brain, to school or athletic performance, and so on. You can teach them about other trusted resources, such as the National Institute on Drug Abuse (NIDA), which has a resource specifically for teens (teens.drugabuse.gov).
For your high school students and those heading off to college, provide a safe place to talk about what they have tried and whether they (or you) have any worries about substance use. You have a unique combination of clinical authority and expertise in them as individuals, and can help them meaningfully plan how to handle their choices. You might talk about the specific risks of binge drinking, from sexual assault to alcohol poisoning and permanent cognitive effects on their developing brains. They also can benefit from hearing about the actual risks of frequent marijuana use, including impaired cognitive performance (and permanent IQ decline), and ongoing risks to their still-developing brains. Don’t be surprised if your older adolescent patients want to educate you about risks. Be curious and humble, and don’t be afraid to go together to a third party for information. You should encourage their efforts to think critically, and be empathic to their dilemma as they try to balance risks against their drive to have new experiences, to be independent, and to be strongly connected to their peers.
Adolescents should hear about your concern about their specific risks with drugs and alcohol, such as a history of traumatic brain injury (concussion), a family history of drug or alcohol dependence, or their own diagnosis of anxiety, depression, or ADHD. You might point out that because they have not tried any drugs or alcohol in high school, they may be prone to having too much to drink when they first try it. Or you might observe that because they have an anxiety disorder, they are vulnerable to becoming dependent on alcohol. Hearing about their specific level of risk equips them to make wiser choices in the context of their growing autonomy.
Prevention efforts you can make: To the parents
Your other prevention strategies should include parents. Studies have shown that when parents have clear rules and expectations about drug and alcohol use, and are consistent about enforcing consequences in their home, their children are significantly less likely than their peers to have experimented with drugs or alcohol by their senior year in high school. Parents of children headed to middle school should hear about this fact, alongside accurate information about the risks associated with alcohol and specific drugs for the developing brain.
Finally, parents need to hear that they can be effective disciplinarians, while also making clear to their children that safety comes first, and that their rules should have clear exceptions for safety. If the parents have a rule against any use of alcohol or drugs, there should be an exception if their child is out and feels unsafe. If they are drunk, or their driver has been drinking, they can call for a ride and will not be in (much) trouble. Rules don’t have to be draconian to be effective; they should always support honesty and safety first. This is a lot of territory to cover, and you do not have to be the only resource for parents. Reliable online resources, such as NIDA’s and SAMHSA’s websites, are full of useful information, and others, such as teen-safe.org, have detailed resources for parents in particular.
References
1. Hum Genet. 2012 Jun;131(6):779-89.
2. Alcohol Clin Exp Res. 2013 Jan;37(Suppl 1):E281-90.
Dr. Swick is an attending psychiatrist in the division of child psychiatry at Massachusetts General Hospital, Boston, and director of the Parenting at a Challenging Time (PACT) Program at the Vernon Cancer Center at Newton Wellesley Hospital, also in Boston. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston.
Interferon Beta May Reduce Mortality in MS
PARIS—Interferon beta is associated with a lower risk of all-cause mortality among patients with multiple sclerosis (MS) treated in clinical practice, according to data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Participants in the study were observed for as long as 18 years. The findings were consistent across two geographically distinct regions (ie, Canada and France), said the investigators.
Interferon beta has benefits for patients with MS, but whether the treatment prolongs survival in this population is unclear. Elaine Kingwell, PhD, a research associate in the Division of Neurology at the University of British Columbia in Vancouver, and colleagues investigated the association between interferon beta treatment and all-cause mortality in the clinical setting.
The researchers accessed prospectively collected data on patients with relapsing-remitting MS at onset, including sex, birth date, Expanded Disability Status Scale (EDSS) scores, and disease modifying treatments (DMTs), from British Columbia, Canada, and Rennes, France. Data were linked to population-based administrative databases capturing death dates in both countries. In Canada, data about drug prescriptions filled, universal health care registration, hospital admissions, and physician visits also were available. Patients were treatment-naïve at study entry, and investigators followed them from the earliest of first MS clinic visit, 18th birthday, or January 1, 1996, to the earliest of death, emigration, or December 31, 2013.
Using a nested case–control design, the researchers randomly selected as many as 20 MS controls by incidence density sampling and matched them to MS cases (ie, patients who died during follow-up) by sex, age (± 5 years), calendar year, and EDSS score at study entry. The association between all-cause mortality and interferon beta exposure (greater than six months) was estimated by conditional logistic regression, expressed as odds ratios (OR), and adjusted for glatiramer acetate (greater than six months exposure), any exposure to another DMT, age, and comorbidity burden. Analyses were stratified by sex and country. The researchers examined the association with cumulative exposure to interferon beta (up to three years or more than three years).
The cohort included 7,009 patients (75% women) with relapsing-remitting MS with a median age at study entry of 42. During follow-up (median, 12.3 years), 30% of participants were exposed to interferon beta, 11% were exposed to glatiramer acetate, and 12% were exposed to other DMTs, including MS-specific immunosuppressants. As many as 20 controls were successfully matched to each of 649 cases (mean age at death, 60). The odds of exposure to interferon beta was 32% lower among cases than controls. Stratification by sex or country did not change the interpretation of findings. Compared with no or minimal exposure, a longer cumulative time on interferon beta (ie, more than three years) was associated with increased survival (OR, 0.44), whereas exposure of less than three years was not (OR, 1.00).
PARIS—Interferon beta is associated with a lower risk of all-cause mortality among patients with multiple sclerosis (MS) treated in clinical practice, according to data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Participants in the study were observed for as long as 18 years. The findings were consistent across two geographically distinct regions (ie, Canada and France), said the investigators.
Interferon beta has benefits for patients with MS, but whether the treatment prolongs survival in this population is unclear. Elaine Kingwell, PhD, a research associate in the Division of Neurology at the University of British Columbia in Vancouver, and colleagues investigated the association between interferon beta treatment and all-cause mortality in the clinical setting.
The researchers accessed prospectively collected data on patients with relapsing-remitting MS at onset, including sex, birth date, Expanded Disability Status Scale (EDSS) scores, and disease modifying treatments (DMTs), from British Columbia, Canada, and Rennes, France. Data were linked to population-based administrative databases capturing death dates in both countries. In Canada, data about drug prescriptions filled, universal health care registration, hospital admissions, and physician visits also were available. Patients were treatment-naïve at study entry, and investigators followed them from the earliest of first MS clinic visit, 18th birthday, or January 1, 1996, to the earliest of death, emigration, or December 31, 2013.
Using a nested case–control design, the researchers randomly selected as many as 20 MS controls by incidence density sampling and matched them to MS cases (ie, patients who died during follow-up) by sex, age (± 5 years), calendar year, and EDSS score at study entry. The association between all-cause mortality and interferon beta exposure (greater than six months) was estimated by conditional logistic regression, expressed as odds ratios (OR), and adjusted for glatiramer acetate (greater than six months exposure), any exposure to another DMT, age, and comorbidity burden. Analyses were stratified by sex and country. The researchers examined the association with cumulative exposure to interferon beta (up to three years or more than three years).
The cohort included 7,009 patients (75% women) with relapsing-remitting MS with a median age at study entry of 42. During follow-up (median, 12.3 years), 30% of participants were exposed to interferon beta, 11% were exposed to glatiramer acetate, and 12% were exposed to other DMTs, including MS-specific immunosuppressants. As many as 20 controls were successfully matched to each of 649 cases (mean age at death, 60). The odds of exposure to interferon beta was 32% lower among cases than controls. Stratification by sex or country did not change the interpretation of findings. Compared with no or minimal exposure, a longer cumulative time on interferon beta (ie, more than three years) was associated with increased survival (OR, 0.44), whereas exposure of less than three years was not (OR, 1.00).
PARIS—Interferon beta is associated with a lower risk of all-cause mortality among patients with multiple sclerosis (MS) treated in clinical practice, according to data presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. Participants in the study were observed for as long as 18 years. The findings were consistent across two geographically distinct regions (ie, Canada and France), said the investigators.
Interferon beta has benefits for patients with MS, but whether the treatment prolongs survival in this population is unclear. Elaine Kingwell, PhD, a research associate in the Division of Neurology at the University of British Columbia in Vancouver, and colleagues investigated the association between interferon beta treatment and all-cause mortality in the clinical setting.
The researchers accessed prospectively collected data on patients with relapsing-remitting MS at onset, including sex, birth date, Expanded Disability Status Scale (EDSS) scores, and disease modifying treatments (DMTs), from British Columbia, Canada, and Rennes, France. Data were linked to population-based administrative databases capturing death dates in both countries. In Canada, data about drug prescriptions filled, universal health care registration, hospital admissions, and physician visits also were available. Patients were treatment-naïve at study entry, and investigators followed them from the earliest of first MS clinic visit, 18th birthday, or January 1, 1996, to the earliest of death, emigration, or December 31, 2013.
Using a nested case–control design, the researchers randomly selected as many as 20 MS controls by incidence density sampling and matched them to MS cases (ie, patients who died during follow-up) by sex, age (± 5 years), calendar year, and EDSS score at study entry. The association between all-cause mortality and interferon beta exposure (greater than six months) was estimated by conditional logistic regression, expressed as odds ratios (OR), and adjusted for glatiramer acetate (greater than six months exposure), any exposure to another DMT, age, and comorbidity burden. Analyses were stratified by sex and country. The researchers examined the association with cumulative exposure to interferon beta (up to three years or more than three years).
The cohort included 7,009 patients (75% women) with relapsing-remitting MS with a median age at study entry of 42. During follow-up (median, 12.3 years), 30% of participants were exposed to interferon beta, 11% were exposed to glatiramer acetate, and 12% were exposed to other DMTs, including MS-specific immunosuppressants. As many as 20 controls were successfully matched to each of 649 cases (mean age at death, 60). The odds of exposure to interferon beta was 32% lower among cases than controls. Stratification by sex or country did not change the interpretation of findings. Compared with no or minimal exposure, a longer cumulative time on interferon beta (ie, more than three years) was associated with increased survival (OR, 0.44), whereas exposure of less than three years was not (OR, 1.00).
More to psychiatry than just neuroscience; The impact of childhood trauma
More to psychiatry than just neuroscience
In his editorial “Advancing clinical neuroscience literacy among psychiatric practitioners” (From the Editor,
I find that many of my patients look for more or different drugs to fix their dysfunctional patterns in life—many of which stem from their dysfunctional and traumatic childhoods. Thus, it is more than just drugs and neurochemical pathways, more than just the “dysregulated neural circuitry,” that we need to focus on in our psychiatric practice.
I finished my psychiatric residency in 1972, before we knew much about neuroscience. Since then, we have learned so much about neuroscience and the specific neuroscience mechanisms involved in the brain and mind. Those advances have done much to aid our core understanding of psychiatric disorders. However, let us not forget that there is more to the mind than just neurochemistry, and more to our practice of psychiatry than just neuroscience.
Leonard Korn, MD
Psychiatrist
Portsmouth Regional Hospital
Portsmouth, New Hampshire
Dr. Nasrallah responds
It is now widely accepted in our field that all psychological phenomena and all human behaviors are associated with neurobiological components. All life events, especially traumatic experiences, are transduced into structural and chemical changes, often within minutes. The formation of dendritic spines to encode the memory of one’s experiences throughout waking hours is well established in neuroscience, and hundreds of studies have been published about this.
Psychotherapy is a neurobiological intervention that induces neuroplasticity and leads to structural brain repair, because talking, listening, triggering memories, inducing insight, and “connecting the dots” in one’s behavior are all biological events.1,2 There is no such thing as a purely psychological process independent of the brain. The mind is the product of ongoing complex, intricate activity of brain neurocircuits whose neurobiological activity is translated into thoughts, emotions, impulses, and behaviors. The mind is perpetually tethered to its neurological roots.
Thus, reductionism actually describes a scientific fact and is not a term with pejorative connotations used to shut down scientific discourse about the biological basis of human behavior. By advancing their clinical neuroscience literacy, psychiatric practitioners will understand that they deal with a specific brain pathology in every patient that they treat and that the medications and psychotherapeutic interventions they employ are synergistic biological treatments.3
Henry A. Nasrallah, MD
Professor and Chair
Department of Psychiatry and Behavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri
References
1. Nasrallah HA. Repositioning psychotherapy as a neurobiological intervention. Current Psychiatry. 2013;12(12):18-19.
2. Nasrallah HA. Out-of-the-box questions about psychotherapy. Current Psychiatry. 2010;9(10):13-14.
3. Nasrallah HA. Medications with psychotherapy: a synergy to heal the brain. C urrent Psychiatry. 2006;5(10):11-12.
The impact of childhood trauma
I enjoyed Dr. Nasrallah’s article “Beyond DSM-5: Clinical and biologic features shared by major psychiatric syndromes” (From the Editor, Current Psychiatry. October 2017, p. 4,6-7), but there was only 1 mention of childhood trauma, which shares features with most of the commonalities he described, such as inflammation, smaller brain volumes, gene and environment interaction, shortened telomeres, and elevated cortisol levels. The Adverse Childhood Experiences Study1 taught us about the impact of childhood trauma on the entire organism. We need to focus on that commonality.
Susan Jones, MD
Child and Adolescent Psychiatrist
Virginia Treatment Center for Children
Assistant Professor
Virginia Commonwealth University
School of Medicine
Richmond, Virginia
Reference
1. Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14(4):245-258
Dr. Nasrallah responds
It is worth pointing out that childhood trauma predominantly leads to psychotic and mood disorders in adulthood, and the criteria I mentioned would then hold true.
More to psychiatry than just neuroscience
In his editorial “Advancing clinical neuroscience literacy among psychiatric practitioners” (From the Editor,
I find that many of my patients look for more or different drugs to fix their dysfunctional patterns in life—many of which stem from their dysfunctional and traumatic childhoods. Thus, it is more than just drugs and neurochemical pathways, more than just the “dysregulated neural circuitry,” that we need to focus on in our psychiatric practice.
I finished my psychiatric residency in 1972, before we knew much about neuroscience. Since then, we have learned so much about neuroscience and the specific neuroscience mechanisms involved in the brain and mind. Those advances have done much to aid our core understanding of psychiatric disorders. However, let us not forget that there is more to the mind than just neurochemistry, and more to our practice of psychiatry than just neuroscience.
Leonard Korn, MD
Psychiatrist
Portsmouth Regional Hospital
Portsmouth, New Hampshire
Dr. Nasrallah responds
It is now widely accepted in our field that all psychological phenomena and all human behaviors are associated with neurobiological components. All life events, especially traumatic experiences, are transduced into structural and chemical changes, often within minutes. The formation of dendritic spines to encode the memory of one’s experiences throughout waking hours is well established in neuroscience, and hundreds of studies have been published about this.
Psychotherapy is a neurobiological intervention that induces neuroplasticity and leads to structural brain repair, because talking, listening, triggering memories, inducing insight, and “connecting the dots” in one’s behavior are all biological events.1,2 There is no such thing as a purely psychological process independent of the brain. The mind is the product of ongoing complex, intricate activity of brain neurocircuits whose neurobiological activity is translated into thoughts, emotions, impulses, and behaviors. The mind is perpetually tethered to its neurological roots.
Thus, reductionism actually describes a scientific fact and is not a term with pejorative connotations used to shut down scientific discourse about the biological basis of human behavior. By advancing their clinical neuroscience literacy, psychiatric practitioners will understand that they deal with a specific brain pathology in every patient that they treat and that the medications and psychotherapeutic interventions they employ are synergistic biological treatments.3
Henry A. Nasrallah, MD
Professor and Chair
Department of Psychiatry and Behavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri
References
1. Nasrallah HA. Repositioning psychotherapy as a neurobiological intervention. Current Psychiatry. 2013;12(12):18-19.
2. Nasrallah HA. Out-of-the-box questions about psychotherapy. Current Psychiatry. 2010;9(10):13-14.
3. Nasrallah HA. Medications with psychotherapy: a synergy to heal the brain. C urrent Psychiatry. 2006;5(10):11-12.
The impact of childhood trauma
I enjoyed Dr. Nasrallah’s article “Beyond DSM-5: Clinical and biologic features shared by major psychiatric syndromes” (From the Editor, Current Psychiatry. October 2017, p. 4,6-7), but there was only 1 mention of childhood trauma, which shares features with most of the commonalities he described, such as inflammation, smaller brain volumes, gene and environment interaction, shortened telomeres, and elevated cortisol levels. The Adverse Childhood Experiences Study1 taught us about the impact of childhood trauma on the entire organism. We need to focus on that commonality.
Susan Jones, MD
Child and Adolescent Psychiatrist
Virginia Treatment Center for Children
Assistant Professor
Virginia Commonwealth University
School of Medicine
Richmond, Virginia
Reference
1. Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14(4):245-258
Dr. Nasrallah responds
It is worth pointing out that childhood trauma predominantly leads to psychotic and mood disorders in adulthood, and the criteria I mentioned would then hold true.
More to psychiatry than just neuroscience
In his editorial “Advancing clinical neuroscience literacy among psychiatric practitioners” (From the Editor,
I find that many of my patients look for more or different drugs to fix their dysfunctional patterns in life—many of which stem from their dysfunctional and traumatic childhoods. Thus, it is more than just drugs and neurochemical pathways, more than just the “dysregulated neural circuitry,” that we need to focus on in our psychiatric practice.
I finished my psychiatric residency in 1972, before we knew much about neuroscience. Since then, we have learned so much about neuroscience and the specific neuroscience mechanisms involved in the brain and mind. Those advances have done much to aid our core understanding of psychiatric disorders. However, let us not forget that there is more to the mind than just neurochemistry, and more to our practice of psychiatry than just neuroscience.
Leonard Korn, MD
Psychiatrist
Portsmouth Regional Hospital
Portsmouth, New Hampshire
Dr. Nasrallah responds
It is now widely accepted in our field that all psychological phenomena and all human behaviors are associated with neurobiological components. All life events, especially traumatic experiences, are transduced into structural and chemical changes, often within minutes. The formation of dendritic spines to encode the memory of one’s experiences throughout waking hours is well established in neuroscience, and hundreds of studies have been published about this.
Psychotherapy is a neurobiological intervention that induces neuroplasticity and leads to structural brain repair, because talking, listening, triggering memories, inducing insight, and “connecting the dots” in one’s behavior are all biological events.1,2 There is no such thing as a purely psychological process independent of the brain. The mind is the product of ongoing complex, intricate activity of brain neurocircuits whose neurobiological activity is translated into thoughts, emotions, impulses, and behaviors. The mind is perpetually tethered to its neurological roots.
Thus, reductionism actually describes a scientific fact and is not a term with pejorative connotations used to shut down scientific discourse about the biological basis of human behavior. By advancing their clinical neuroscience literacy, psychiatric practitioners will understand that they deal with a specific brain pathology in every patient that they treat and that the medications and psychotherapeutic interventions they employ are synergistic biological treatments.3
Henry A. Nasrallah, MD
Professor and Chair
Department of Psychiatry and Behavioral Neuroscience
Saint Louis University School of Medicine
St. Louis, Missouri
References
1. Nasrallah HA. Repositioning psychotherapy as a neurobiological intervention. Current Psychiatry. 2013;12(12):18-19.
2. Nasrallah HA. Out-of-the-box questions about psychotherapy. Current Psychiatry. 2010;9(10):13-14.
3. Nasrallah HA. Medications with psychotherapy: a synergy to heal the brain. C urrent Psychiatry. 2006;5(10):11-12.
The impact of childhood trauma
I enjoyed Dr. Nasrallah’s article “Beyond DSM-5: Clinical and biologic features shared by major psychiatric syndromes” (From the Editor, Current Psychiatry. October 2017, p. 4,6-7), but there was only 1 mention of childhood trauma, which shares features with most of the commonalities he described, such as inflammation, smaller brain volumes, gene and environment interaction, shortened telomeres, and elevated cortisol levels. The Adverse Childhood Experiences Study1 taught us about the impact of childhood trauma on the entire organism. We need to focus on that commonality.
Susan Jones, MD
Child and Adolescent Psychiatrist
Virginia Treatment Center for Children
Assistant Professor
Virginia Commonwealth University
School of Medicine
Richmond, Virginia
Reference
1. Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The Adverse Childhood Experiences (ACE) Study. Am J Prev Med. 1998;14(4):245-258
Dr. Nasrallah responds
It is worth pointing out that childhood trauma predominantly leads to psychotic and mood disorders in adulthood, and the criteria I mentioned would then hold true.
FDA grants orphan drug status to rofecoxib for hemophilic arthropathy
The Food and Drug Administration on Nov. 21 granted orphan drug designation to rofecoxib (TRM-201), a cyclooxygenase 2–selective nonsteroidal anti-inflammatory drug (NSAID) intended to treat patients with hemophilic arthropathy (HA).
HA, a joint disease caused by hemarthrosis, is the largest cause of morbidity for hemophilia patients. There are currently no approved treatments in the United States.
The attempt at a reintroduction of rofecoxib specifically for the treatment of HA is being developed by Tremeau Pharmaceuticals.
Patients with hemophilia look to avoid traditional NSAIDs, as those drugs risk gastrointestinal ulcers and impair platelet aggregation. The current standard of care for HA is opioid treatment.
Rofecoxib and other NSAIDs cause an increased risk of serious cardiovascular thrombotic events and gastrointestinal adverse events.
Orphan drug status is available to treatments for rare disorders and provides a 7-year marketing exclusivity period against competition, along with tax credits and a waiver of Prescription Drug User Fee Act filing fees.
The Food and Drug Administration on Nov. 21 granted orphan drug designation to rofecoxib (TRM-201), a cyclooxygenase 2–selective nonsteroidal anti-inflammatory drug (NSAID) intended to treat patients with hemophilic arthropathy (HA).
HA, a joint disease caused by hemarthrosis, is the largest cause of morbidity for hemophilia patients. There are currently no approved treatments in the United States.
The attempt at a reintroduction of rofecoxib specifically for the treatment of HA is being developed by Tremeau Pharmaceuticals.
Patients with hemophilia look to avoid traditional NSAIDs, as those drugs risk gastrointestinal ulcers and impair platelet aggregation. The current standard of care for HA is opioid treatment.
Rofecoxib and other NSAIDs cause an increased risk of serious cardiovascular thrombotic events and gastrointestinal adverse events.
Orphan drug status is available to treatments for rare disorders and provides a 7-year marketing exclusivity period against competition, along with tax credits and a waiver of Prescription Drug User Fee Act filing fees.
The Food and Drug Administration on Nov. 21 granted orphan drug designation to rofecoxib (TRM-201), a cyclooxygenase 2–selective nonsteroidal anti-inflammatory drug (NSAID) intended to treat patients with hemophilic arthropathy (HA).
HA, a joint disease caused by hemarthrosis, is the largest cause of morbidity for hemophilia patients. There are currently no approved treatments in the United States.
The attempt at a reintroduction of rofecoxib specifically for the treatment of HA is being developed by Tremeau Pharmaceuticals.
Patients with hemophilia look to avoid traditional NSAIDs, as those drugs risk gastrointestinal ulcers and impair platelet aggregation. The current standard of care for HA is opioid treatment.
Rofecoxib and other NSAIDs cause an increased risk of serious cardiovascular thrombotic events and gastrointestinal adverse events.
Orphan drug status is available to treatments for rare disorders and provides a 7-year marketing exclusivity period against competition, along with tax credits and a waiver of Prescription Drug User Fee Act filing fees.