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Researchers win Stand Up To Cancer grants
Stand Up To Cancer has awarded 1- and 2-year grants to five teams conducting cancer research.
Alan D’Andrea, MD, of the Dana-Farber Cancer Institute in Boston and Juan Cubillos-Ruiz, PhD, of Weill Cornell Medicine in New York won a 2-year grant totaling $250,000.
Dr. Cubillos-Ruiz and Dr. D’Andrea will use this funding to evaluate gene signatures controlled by phospholipid messengers and endoplasmic reticulum stress in responding and nonresponding ovarian cancer patients, and the team will use tumor organoids to test whether pharmacological inhibition of these pathways can fight ovarian cancer.
Denada Dibra, PhD, of the University of Texas MD Anderson Cancer Center in Houston and Peter Lee, MD, of City of Hope in Duarte, Calif., won a 1-year grant of $250,000.
Dr. Lee and Dr. Dibra will use mouse models to study how TP53 may influence the tumor microenvironment in triple-negative breast cancer and to characterize tumor cells and immune cells in the tumor tissue.
Maximilian Diehn, MD, PhD, of Stanford (Calif.) University and Aaron Hata, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston won a 2-year grant totaling $225,000.
Dr. Hata and Dr. Diehn will work on developing a novel method for analyzing cell-free RNA associated with resistance to tyrosine kinase inhibitors in patients with non–small cell lung cancer. The team’s goal is to develop a noninvasive approach to better characterize tumors and detect phenotypic changes during treatment.
Sarah Tasian, MD, of Children’s Hospital of Philadelphia and Kimberly Stegmaier, MD, of the Dana-Farber Cancer Institute won a 2-year grant totaling $250,000, which was funded with support from the Emily Whitehead Foundation.
Dr. Stegmaier and Dr. Tasian will test chimeric antigen receptor T cells targeting two or more neoantigens in preclinical models of childhood Down syndrome–associated acute lymphoblastic leukemia and Ph-like acute lymphoblastic leukemia.
Robert Vonderheide, MD, of the University of Pennsylvania Abramson Cancer Center in Philadelphia and Vinod Balachandran, MD, of Memorial Sloan Kettering Cancer Center in New York won a 2-year grant totaling $225,000.
Dr. Balachandran and Dr. Vonderheide will analyze short- and long-term pancreatic cancer survivors, patients with primary resected pancreatic cancers and patients with mKRAS lung and colon cancers to evaluate how mKRAS immunogenicity may affect outcomes.
Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected], and you could be featured in Movers in Medicine.
Stand Up To Cancer has awarded 1- and 2-year grants to five teams conducting cancer research.
Alan D’Andrea, MD, of the Dana-Farber Cancer Institute in Boston and Juan Cubillos-Ruiz, PhD, of Weill Cornell Medicine in New York won a 2-year grant totaling $250,000.
Dr. Cubillos-Ruiz and Dr. D’Andrea will use this funding to evaluate gene signatures controlled by phospholipid messengers and endoplasmic reticulum stress in responding and nonresponding ovarian cancer patients, and the team will use tumor organoids to test whether pharmacological inhibition of these pathways can fight ovarian cancer.
Denada Dibra, PhD, of the University of Texas MD Anderson Cancer Center in Houston and Peter Lee, MD, of City of Hope in Duarte, Calif., won a 1-year grant of $250,000.
Dr. Lee and Dr. Dibra will use mouse models to study how TP53 may influence the tumor microenvironment in triple-negative breast cancer and to characterize tumor cells and immune cells in the tumor tissue.
Maximilian Diehn, MD, PhD, of Stanford (Calif.) University and Aaron Hata, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston won a 2-year grant totaling $225,000.
Dr. Hata and Dr. Diehn will work on developing a novel method for analyzing cell-free RNA associated with resistance to tyrosine kinase inhibitors in patients with non–small cell lung cancer. The team’s goal is to develop a noninvasive approach to better characterize tumors and detect phenotypic changes during treatment.
Sarah Tasian, MD, of Children’s Hospital of Philadelphia and Kimberly Stegmaier, MD, of the Dana-Farber Cancer Institute won a 2-year grant totaling $250,000, which was funded with support from the Emily Whitehead Foundation.
Dr. Stegmaier and Dr. Tasian will test chimeric antigen receptor T cells targeting two or more neoantigens in preclinical models of childhood Down syndrome–associated acute lymphoblastic leukemia and Ph-like acute lymphoblastic leukemia.
Robert Vonderheide, MD, of the University of Pennsylvania Abramson Cancer Center in Philadelphia and Vinod Balachandran, MD, of Memorial Sloan Kettering Cancer Center in New York won a 2-year grant totaling $225,000.
Dr. Balachandran and Dr. Vonderheide will analyze short- and long-term pancreatic cancer survivors, patients with primary resected pancreatic cancers and patients with mKRAS lung and colon cancers to evaluate how mKRAS immunogenicity may affect outcomes.
Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected], and you could be featured in Movers in Medicine.
Stand Up To Cancer has awarded 1- and 2-year grants to five teams conducting cancer research.
Alan D’Andrea, MD, of the Dana-Farber Cancer Institute in Boston and Juan Cubillos-Ruiz, PhD, of Weill Cornell Medicine in New York won a 2-year grant totaling $250,000.
Dr. Cubillos-Ruiz and Dr. D’Andrea will use this funding to evaluate gene signatures controlled by phospholipid messengers and endoplasmic reticulum stress in responding and nonresponding ovarian cancer patients, and the team will use tumor organoids to test whether pharmacological inhibition of these pathways can fight ovarian cancer.
Denada Dibra, PhD, of the University of Texas MD Anderson Cancer Center in Houston and Peter Lee, MD, of City of Hope in Duarte, Calif., won a 1-year grant of $250,000.
Dr. Lee and Dr. Dibra will use mouse models to study how TP53 may influence the tumor microenvironment in triple-negative breast cancer and to characterize tumor cells and immune cells in the tumor tissue.
Maximilian Diehn, MD, PhD, of Stanford (Calif.) University and Aaron Hata, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston won a 2-year grant totaling $225,000.
Dr. Hata and Dr. Diehn will work on developing a novel method for analyzing cell-free RNA associated with resistance to tyrosine kinase inhibitors in patients with non–small cell lung cancer. The team’s goal is to develop a noninvasive approach to better characterize tumors and detect phenotypic changes during treatment.
Sarah Tasian, MD, of Children’s Hospital of Philadelphia and Kimberly Stegmaier, MD, of the Dana-Farber Cancer Institute won a 2-year grant totaling $250,000, which was funded with support from the Emily Whitehead Foundation.
Dr. Stegmaier and Dr. Tasian will test chimeric antigen receptor T cells targeting two or more neoantigens in preclinical models of childhood Down syndrome–associated acute lymphoblastic leukemia and Ph-like acute lymphoblastic leukemia.
Robert Vonderheide, MD, of the University of Pennsylvania Abramson Cancer Center in Philadelphia and Vinod Balachandran, MD, of Memorial Sloan Kettering Cancer Center in New York won a 2-year grant totaling $225,000.
Dr. Balachandran and Dr. Vonderheide will analyze short- and long-term pancreatic cancer survivors, patients with primary resected pancreatic cancers and patients with mKRAS lung and colon cancers to evaluate how mKRAS immunogenicity may affect outcomes.
Movers in Medicine highlights career moves and personal achievements by hematologists and oncologists. Did you switch jobs, take on a new role, climb a mountain? Tell us all about it at [email protected], and you could be featured in Movers in Medicine.
Interplay of TP53, ESR2 may expand treatment options for some TNBCs
, an interaction that may have therapeutic implications for triple-negative disease, a new study suggests.
Up to 80% of triple-negative breast cancers (TNBCs) express ESR2, but its role has been hard to pin down because of conflicting data, according to the investigators, who were led by senior author Gokul M. Das, PhD, of the department of pharmacology and therapeutics, Center for Genetics and Pharmacology, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y. Expression has been found to have both antiproliferative activity and proproliferative activity, depending on the experimental conditions.
Dr. Das and colleagues performed a series of in vitro assays in breast cancer cell lines and a clinical study of patients with basal-like TNBC from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort (308 patients with TP53 mutational status determined by sequencing) and a Roswell cohort (46 patients with TP53 mutational status determined by immunohistochemistry).
Results showed that in vitro, ESR2 interaction with wild-type TP53 had proproliferative effects, whereas interaction of ESR2 with mutant TP53 had antiproliferative effects. The report is in the Journal of the National Cancer Institute.
In luminal breast cancer cell lines with wild-type TP53, compared with control, depleting ESR2 increased expression of the TP53 target genes CDKN1A and BBC3 (P = .003 and P = .003, respectively); in contrast, in those with mutant TP53, depleting ESR2 decreased their expression (P = .02 and P = .008). Opposite results were seen when ESR2 was instead overexpressed.
In cells with mutant TP53, tamoxifen treatment increased interaction of ESR2 with the mutant protein, ultimately leading to reactivation of TP73 and apoptosis.
Finally, among women with basal-like TNBC in the METABRIC cohort, high ESR2 expression was associated with better overall survival for those with mutant TP53 tumors (hazard ratio for death, 0.26) but a trend toward poorer overall survival for those with wild-type TP53 tumors (P = .05). Results were similar in the Roswell cohort.
“These findings suggest that ESR2-TP53 combination can be used to stratify TNBC into therapeutically actionable subgroups,” Dr. Das and coinvestigators proposed.
“Our data that treatment with tamoxifen can lead to sequestration of mutant TP53 away from TP73 and thereby reactivate tumor suppressor activities of TP73, provide for the first time, a strong rationale for suggesting that tamoxifen therapy could be beneficial to basal-type/TNBC patients expressing mutant TP53,” they concluded. “On the other hand, based on our data that ESR2 is proproliferative in the WT [wild-type] TP53 context, we predict that in TNBCs expressing WT TP53, tamoxifen or other agents that increase ESR2-WTP53 interaction may not only be ineffective as antitumor agents, but also may contribute to adverse outcome.”
The authors disclosed that they had no conflicts of interest. The study was supported by the several sources including the National Cancer Institute and Susan G. Komen for the Cure.
SOURCE: Mukhopadhyay UK et al. J Natl Cancer Inst. 2019 Apr 16. doi: 10.1093/jnci/djz051.
“The ability to selectively administer endocrine therapy should, in principle, lead to greater response rates,” according to an editorial by Sunil Badve, MBBS, FRCPath, and Yesim Gokmen-Polar, PhD (J Natl Cancer Inst. 2019 Apr 16. doi: 10.1093/jnci/djz052).
The study illustrates that “company matters” when it comes to the impact of markers and mutations in cancers, they maintain. “The intracellular environment is a complex milieu wherein changes in one player can have a dramatic impact on DNA, RNA and protein interactions. The players in the neighborhood could further affect cellular phenotype.
“Acknowledging these processes also provides a reality check for those of us involved in precision medicine, wherein treatments are being prescribed based on the presence of single gene mutations ... ” Dr. Badve and Dr. Gokmen-Polar noted. “The cooperativity and interactions of cellular networks may, to a large extent, determine the prognostic and predictive utility of mutations in patients.”
The new study “is a good step in this direction and provides compelling reasons to understand the combinatorial impact to determine clinically actionable strategies and solutions,” they concluded.
Dr. Badve and Dr. Gokmen-Polar are in the department of pathology and laboratory medicine at Indiana University, Indianapolis.
“The ability to selectively administer endocrine therapy should, in principle, lead to greater response rates,” according to an editorial by Sunil Badve, MBBS, FRCPath, and Yesim Gokmen-Polar, PhD (J Natl Cancer Inst. 2019 Apr 16. doi: 10.1093/jnci/djz052).
The study illustrates that “company matters” when it comes to the impact of markers and mutations in cancers, they maintain. “The intracellular environment is a complex milieu wherein changes in one player can have a dramatic impact on DNA, RNA and protein interactions. The players in the neighborhood could further affect cellular phenotype.
“Acknowledging these processes also provides a reality check for those of us involved in precision medicine, wherein treatments are being prescribed based on the presence of single gene mutations ... ” Dr. Badve and Dr. Gokmen-Polar noted. “The cooperativity and interactions of cellular networks may, to a large extent, determine the prognostic and predictive utility of mutations in patients.”
The new study “is a good step in this direction and provides compelling reasons to understand the combinatorial impact to determine clinically actionable strategies and solutions,” they concluded.
Dr. Badve and Dr. Gokmen-Polar are in the department of pathology and laboratory medicine at Indiana University, Indianapolis.
“The ability to selectively administer endocrine therapy should, in principle, lead to greater response rates,” according to an editorial by Sunil Badve, MBBS, FRCPath, and Yesim Gokmen-Polar, PhD (J Natl Cancer Inst. 2019 Apr 16. doi: 10.1093/jnci/djz052).
The study illustrates that “company matters” when it comes to the impact of markers and mutations in cancers, they maintain. “The intracellular environment is a complex milieu wherein changes in one player can have a dramatic impact on DNA, RNA and protein interactions. The players in the neighborhood could further affect cellular phenotype.
“Acknowledging these processes also provides a reality check for those of us involved in precision medicine, wherein treatments are being prescribed based on the presence of single gene mutations ... ” Dr. Badve and Dr. Gokmen-Polar noted. “The cooperativity and interactions of cellular networks may, to a large extent, determine the prognostic and predictive utility of mutations in patients.”
The new study “is a good step in this direction and provides compelling reasons to understand the combinatorial impact to determine clinically actionable strategies and solutions,” they concluded.
Dr. Badve and Dr. Gokmen-Polar are in the department of pathology and laboratory medicine at Indiana University, Indianapolis.
, an interaction that may have therapeutic implications for triple-negative disease, a new study suggests.
Up to 80% of triple-negative breast cancers (TNBCs) express ESR2, but its role has been hard to pin down because of conflicting data, according to the investigators, who were led by senior author Gokul M. Das, PhD, of the department of pharmacology and therapeutics, Center for Genetics and Pharmacology, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y. Expression has been found to have both antiproliferative activity and proproliferative activity, depending on the experimental conditions.
Dr. Das and colleagues performed a series of in vitro assays in breast cancer cell lines and a clinical study of patients with basal-like TNBC from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort (308 patients with TP53 mutational status determined by sequencing) and a Roswell cohort (46 patients with TP53 mutational status determined by immunohistochemistry).
Results showed that in vitro, ESR2 interaction with wild-type TP53 had proproliferative effects, whereas interaction of ESR2 with mutant TP53 had antiproliferative effects. The report is in the Journal of the National Cancer Institute.
In luminal breast cancer cell lines with wild-type TP53, compared with control, depleting ESR2 increased expression of the TP53 target genes CDKN1A and BBC3 (P = .003 and P = .003, respectively); in contrast, in those with mutant TP53, depleting ESR2 decreased their expression (P = .02 and P = .008). Opposite results were seen when ESR2 was instead overexpressed.
In cells with mutant TP53, tamoxifen treatment increased interaction of ESR2 with the mutant protein, ultimately leading to reactivation of TP73 and apoptosis.
Finally, among women with basal-like TNBC in the METABRIC cohort, high ESR2 expression was associated with better overall survival for those with mutant TP53 tumors (hazard ratio for death, 0.26) but a trend toward poorer overall survival for those with wild-type TP53 tumors (P = .05). Results were similar in the Roswell cohort.
“These findings suggest that ESR2-TP53 combination can be used to stratify TNBC into therapeutically actionable subgroups,” Dr. Das and coinvestigators proposed.
“Our data that treatment with tamoxifen can lead to sequestration of mutant TP53 away from TP73 and thereby reactivate tumor suppressor activities of TP73, provide for the first time, a strong rationale for suggesting that tamoxifen therapy could be beneficial to basal-type/TNBC patients expressing mutant TP53,” they concluded. “On the other hand, based on our data that ESR2 is proproliferative in the WT [wild-type] TP53 context, we predict that in TNBCs expressing WT TP53, tamoxifen or other agents that increase ESR2-WTP53 interaction may not only be ineffective as antitumor agents, but also may contribute to adverse outcome.”
The authors disclosed that they had no conflicts of interest. The study was supported by the several sources including the National Cancer Institute and Susan G. Komen for the Cure.
SOURCE: Mukhopadhyay UK et al. J Natl Cancer Inst. 2019 Apr 16. doi: 10.1093/jnci/djz051.
, an interaction that may have therapeutic implications for triple-negative disease, a new study suggests.
Up to 80% of triple-negative breast cancers (TNBCs) express ESR2, but its role has been hard to pin down because of conflicting data, according to the investigators, who were led by senior author Gokul M. Das, PhD, of the department of pharmacology and therapeutics, Center for Genetics and Pharmacology, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y. Expression has been found to have both antiproliferative activity and proproliferative activity, depending on the experimental conditions.
Dr. Das and colleagues performed a series of in vitro assays in breast cancer cell lines and a clinical study of patients with basal-like TNBC from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort (308 patients with TP53 mutational status determined by sequencing) and a Roswell cohort (46 patients with TP53 mutational status determined by immunohistochemistry).
Results showed that in vitro, ESR2 interaction with wild-type TP53 had proproliferative effects, whereas interaction of ESR2 with mutant TP53 had antiproliferative effects. The report is in the Journal of the National Cancer Institute.
In luminal breast cancer cell lines with wild-type TP53, compared with control, depleting ESR2 increased expression of the TP53 target genes CDKN1A and BBC3 (P = .003 and P = .003, respectively); in contrast, in those with mutant TP53, depleting ESR2 decreased their expression (P = .02 and P = .008). Opposite results were seen when ESR2 was instead overexpressed.
In cells with mutant TP53, tamoxifen treatment increased interaction of ESR2 with the mutant protein, ultimately leading to reactivation of TP73 and apoptosis.
Finally, among women with basal-like TNBC in the METABRIC cohort, high ESR2 expression was associated with better overall survival for those with mutant TP53 tumors (hazard ratio for death, 0.26) but a trend toward poorer overall survival for those with wild-type TP53 tumors (P = .05). Results were similar in the Roswell cohort.
“These findings suggest that ESR2-TP53 combination can be used to stratify TNBC into therapeutically actionable subgroups,” Dr. Das and coinvestigators proposed.
“Our data that treatment with tamoxifen can lead to sequestration of mutant TP53 away from TP73 and thereby reactivate tumor suppressor activities of TP73, provide for the first time, a strong rationale for suggesting that tamoxifen therapy could be beneficial to basal-type/TNBC patients expressing mutant TP53,” they concluded. “On the other hand, based on our data that ESR2 is proproliferative in the WT [wild-type] TP53 context, we predict that in TNBCs expressing WT TP53, tamoxifen or other agents that increase ESR2-WTP53 interaction may not only be ineffective as antitumor agents, but also may contribute to adverse outcome.”
The authors disclosed that they had no conflicts of interest. The study was supported by the several sources including the National Cancer Institute and Susan G. Komen for the Cure.
SOURCE: Mukhopadhyay UK et al. J Natl Cancer Inst. 2019 Apr 16. doi: 10.1093/jnci/djz051.
FROM JOURNAL OF THE NATIONAL CANCER INSTITUTE
Key clinical point: In triple-negative breast cancer, TP53 mutational status influences the prognostic impact of estrogen receptor-beta (ESR2) expression.
Major finding: High ESR2 expression was associated with better overall survival among women with mutant TP53 tumors (hazard ratio for death, 0.26) but a trend toward poorer overall survival among women with wild-type TP53 tumors (P = .05).
Study details: In vitro study and retrospective cohort study of 354 women with basal-like triple-negative breast cancer.
Disclosures: The authors disclosed that they had no conflicts of interest. The study was supported by the several sources including the National Cancer Institute and Susan G. Komen for the Cure.
Source: Mukhopadhyay UK et al. J Natl Cancer Inst 2019 Apr 16 doi: 10.1093/jnci/djz051.
Depressive symptoms are associated with stroke risk
PHILADELPHIA – according to preliminary data from a prospective cohort study presented at the annual meeting of the American Academy of Neurology.
Prior research has found that depression may increase the likelihood of hypertension, cardiac morbidity and mortality, and stroke mortality. How depression affects the risk of incident stroke, however, “is underexplored, especially among Latinos and African Americans,” said study author Marialaura Simonetto, MD, of the University of Miami and associates.
To assess the relationship between depressive symptoms and risk of incident ischemic stroke, the researchers analyzed data from more than 1,100 participants in the MRI substudy of the Northern Manhattan Study. The cohort includes older adults who were clinically stroke free at baseline.
Researchers assessed depressive symptoms at baseline using the Center for Epidemiological Studies–Depression Scale (CES-D). Scores range from 0-60, and they considered CES-D scores of 16 or greater to be elevated.
The investigators used Cox proportional hazards models to estimate hazard ratios of incident ischemic stroke after adjusting for age, sex, race, ethnicity, years of education, smoking, physical activity, alcohol consumption, diabetes, and hypertension.
In all, 1,104 participants were included in the analysis. Participants had an average age of 70 years, 61% were women, and 69% were Hispanic. At baseline, 198 participants (18%) had elevated depressive symptoms.
During 14 years of follow-up, 101 participants had incident strokes, 87 of which were ischemic strokes. In adjusted models, participants with elevated depressive symptoms had a significantly greater risk of ischemic stroke (HR, 1.75; 95% confidence interval, 1.06-2.88). “Every 5-point increase in CES-D score conferred a 12% greater risk of ischemic stroke,” the researchers reported.
“Depression is common and often goes untreated,” Dr. Simonetto said in a news release. “If people with depression are at elevated risk of stroke, early detection and treatment will be even more important.”
The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Simonetto reported no disclosures. Coauthors disclosed personal compensation and research support from pharmaceutical and medical device companies.
SOURCE: Simonetto M et al. AAN 2019, Abstract S1.003.
PHILADELPHIA – according to preliminary data from a prospective cohort study presented at the annual meeting of the American Academy of Neurology.
Prior research has found that depression may increase the likelihood of hypertension, cardiac morbidity and mortality, and stroke mortality. How depression affects the risk of incident stroke, however, “is underexplored, especially among Latinos and African Americans,” said study author Marialaura Simonetto, MD, of the University of Miami and associates.
To assess the relationship between depressive symptoms and risk of incident ischemic stroke, the researchers analyzed data from more than 1,100 participants in the MRI substudy of the Northern Manhattan Study. The cohort includes older adults who were clinically stroke free at baseline.
Researchers assessed depressive symptoms at baseline using the Center for Epidemiological Studies–Depression Scale (CES-D). Scores range from 0-60, and they considered CES-D scores of 16 or greater to be elevated.
The investigators used Cox proportional hazards models to estimate hazard ratios of incident ischemic stroke after adjusting for age, sex, race, ethnicity, years of education, smoking, physical activity, alcohol consumption, diabetes, and hypertension.
In all, 1,104 participants were included in the analysis. Participants had an average age of 70 years, 61% were women, and 69% were Hispanic. At baseline, 198 participants (18%) had elevated depressive symptoms.
During 14 years of follow-up, 101 participants had incident strokes, 87 of which were ischemic strokes. In adjusted models, participants with elevated depressive symptoms had a significantly greater risk of ischemic stroke (HR, 1.75; 95% confidence interval, 1.06-2.88). “Every 5-point increase in CES-D score conferred a 12% greater risk of ischemic stroke,” the researchers reported.
“Depression is common and often goes untreated,” Dr. Simonetto said in a news release. “If people with depression are at elevated risk of stroke, early detection and treatment will be even more important.”
The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Simonetto reported no disclosures. Coauthors disclosed personal compensation and research support from pharmaceutical and medical device companies.
SOURCE: Simonetto M et al. AAN 2019, Abstract S1.003.
PHILADELPHIA – according to preliminary data from a prospective cohort study presented at the annual meeting of the American Academy of Neurology.
Prior research has found that depression may increase the likelihood of hypertension, cardiac morbidity and mortality, and stroke mortality. How depression affects the risk of incident stroke, however, “is underexplored, especially among Latinos and African Americans,” said study author Marialaura Simonetto, MD, of the University of Miami and associates.
To assess the relationship between depressive symptoms and risk of incident ischemic stroke, the researchers analyzed data from more than 1,100 participants in the MRI substudy of the Northern Manhattan Study. The cohort includes older adults who were clinically stroke free at baseline.
Researchers assessed depressive symptoms at baseline using the Center for Epidemiological Studies–Depression Scale (CES-D). Scores range from 0-60, and they considered CES-D scores of 16 or greater to be elevated.
The investigators used Cox proportional hazards models to estimate hazard ratios of incident ischemic stroke after adjusting for age, sex, race, ethnicity, years of education, smoking, physical activity, alcohol consumption, diabetes, and hypertension.
In all, 1,104 participants were included in the analysis. Participants had an average age of 70 years, 61% were women, and 69% were Hispanic. At baseline, 198 participants (18%) had elevated depressive symptoms.
During 14 years of follow-up, 101 participants had incident strokes, 87 of which were ischemic strokes. In adjusted models, participants with elevated depressive symptoms had a significantly greater risk of ischemic stroke (HR, 1.75; 95% confidence interval, 1.06-2.88). “Every 5-point increase in CES-D score conferred a 12% greater risk of ischemic stroke,” the researchers reported.
“Depression is common and often goes untreated,” Dr. Simonetto said in a news release. “If people with depression are at elevated risk of stroke, early detection and treatment will be even more important.”
The study was supported by the National Institute of Neurological Disorders and Stroke. Dr. Simonetto reported no disclosures. Coauthors disclosed personal compensation and research support from pharmaceutical and medical device companies.
SOURCE: Simonetto M et al. AAN 2019, Abstract S1.003.
REPORTING FROM AAN 2019
Direct pharmacy dispensing of naloxone linked to drop in fatal overdoses
investigators reported.
By contrast, state laws that stopped short of allowing pharmacists to directly dispense the opioid antagonist did not appear to impact mortality, according to the report, which appears in JAMA Internal Medicine (2019 May 6. doi: 10.1001/jamainternmed.2019.0272).
The report, based on state-level trends tracked from 2005 to 2016, indicates that fatal opioid overdoses fell by nearly one-third in states that adopted direct dispensing laws as compared with states that adopted other naloxone laws.
That finding suggests that the policy type determines whether a naloxone law is useful in combating fatal opioid overdoses, said Rahi Abouk, PhD, of William Paterson University, Wayne, N.J. and co-authors of the paper.
“Enabling distribution through various sources, or requiring gatekeepers, will not be as beneficial,” Dr. Abouk and co-authors said in their report.
The current rate of deaths from fentanyl, heroin, and prescription analgesic overdose has outpaced all previous drug epidemics on record, and even surpasses the number of deaths in the peak year of the HIV epidemic of the 1980s, Dr. Abouk and colleagues wrote in their paper.
The number of states with naloxone access laws grew from just 2 in 2005 to 47 by 2016, including 9 states that granted direct authority to pharmacists and 38 that granted indirect authority, according to the researchers.
The analysis of overdose trends from 2005 to 2016 was based on naloxone distribution data from state Medicaid agencies and opioid-related mortality data from a national statistics system. Forty percent of nonelderly adults with an opioid addiction are covered by Medicaid, the researchers said.
They found that naloxone laws granting pharmacists direct dispensing authority were linked to a drop in opioid deaths that increased in magnitude over time, according to researchers. The mean number of opioid deaths dropped by 27% in the second year after adoption of direct authority laws, relative to opioid deaths in states with indirect access laws, while in subsequent years, deaths dropped by 34%.
Emergency department visits related to opioids increased by 15% in direct authority states 3 or more years after adoption, as compared to states that did not adopt direct authority laws. According to investigators, that translated into 15 additional opioid-related emergency department visits each month.
That increase suggests that, alongside direct dispensing laws, “useful interventions” and connections to treatment are needed for the emergency department, according to Dr. Abouk and colleagues.
“This is the location where such programs may be the most effective,” they said in their report.
Future research should be done to determine whether removing gatekeepers increases the value of naloxone distribution policies, they concluded in the report.
Dr. Abouk had no disclosures. Co-authors on the study reported funding and conflict of interest disclosures related to the National Institute on Drug Abuse and the Centers for Disease Control and Prevention.
SOURCE: Abouk R, et al. JAMA Intern Med. 2019 May 6. doi:10.1001/jamainternmed.2019.0272.
investigators reported.
By contrast, state laws that stopped short of allowing pharmacists to directly dispense the opioid antagonist did not appear to impact mortality, according to the report, which appears in JAMA Internal Medicine (2019 May 6. doi: 10.1001/jamainternmed.2019.0272).
The report, based on state-level trends tracked from 2005 to 2016, indicates that fatal opioid overdoses fell by nearly one-third in states that adopted direct dispensing laws as compared with states that adopted other naloxone laws.
That finding suggests that the policy type determines whether a naloxone law is useful in combating fatal opioid overdoses, said Rahi Abouk, PhD, of William Paterson University, Wayne, N.J. and co-authors of the paper.
“Enabling distribution through various sources, or requiring gatekeepers, will not be as beneficial,” Dr. Abouk and co-authors said in their report.
The current rate of deaths from fentanyl, heroin, and prescription analgesic overdose has outpaced all previous drug epidemics on record, and even surpasses the number of deaths in the peak year of the HIV epidemic of the 1980s, Dr. Abouk and colleagues wrote in their paper.
The number of states with naloxone access laws grew from just 2 in 2005 to 47 by 2016, including 9 states that granted direct authority to pharmacists and 38 that granted indirect authority, according to the researchers.
The analysis of overdose trends from 2005 to 2016 was based on naloxone distribution data from state Medicaid agencies and opioid-related mortality data from a national statistics system. Forty percent of nonelderly adults with an opioid addiction are covered by Medicaid, the researchers said.
They found that naloxone laws granting pharmacists direct dispensing authority were linked to a drop in opioid deaths that increased in magnitude over time, according to researchers. The mean number of opioid deaths dropped by 27% in the second year after adoption of direct authority laws, relative to opioid deaths in states with indirect access laws, while in subsequent years, deaths dropped by 34%.
Emergency department visits related to opioids increased by 15% in direct authority states 3 or more years after adoption, as compared to states that did not adopt direct authority laws. According to investigators, that translated into 15 additional opioid-related emergency department visits each month.
That increase suggests that, alongside direct dispensing laws, “useful interventions” and connections to treatment are needed for the emergency department, according to Dr. Abouk and colleagues.
“This is the location where such programs may be the most effective,” they said in their report.
Future research should be done to determine whether removing gatekeepers increases the value of naloxone distribution policies, they concluded in the report.
Dr. Abouk had no disclosures. Co-authors on the study reported funding and conflict of interest disclosures related to the National Institute on Drug Abuse and the Centers for Disease Control and Prevention.
SOURCE: Abouk R, et al. JAMA Intern Med. 2019 May 6. doi:10.1001/jamainternmed.2019.0272.
investigators reported.
By contrast, state laws that stopped short of allowing pharmacists to directly dispense the opioid antagonist did not appear to impact mortality, according to the report, which appears in JAMA Internal Medicine (2019 May 6. doi: 10.1001/jamainternmed.2019.0272).
The report, based on state-level trends tracked from 2005 to 2016, indicates that fatal opioid overdoses fell by nearly one-third in states that adopted direct dispensing laws as compared with states that adopted other naloxone laws.
That finding suggests that the policy type determines whether a naloxone law is useful in combating fatal opioid overdoses, said Rahi Abouk, PhD, of William Paterson University, Wayne, N.J. and co-authors of the paper.
“Enabling distribution through various sources, or requiring gatekeepers, will not be as beneficial,” Dr. Abouk and co-authors said in their report.
The current rate of deaths from fentanyl, heroin, and prescription analgesic overdose has outpaced all previous drug epidemics on record, and even surpasses the number of deaths in the peak year of the HIV epidemic of the 1980s, Dr. Abouk and colleagues wrote in their paper.
The number of states with naloxone access laws grew from just 2 in 2005 to 47 by 2016, including 9 states that granted direct authority to pharmacists and 38 that granted indirect authority, according to the researchers.
The analysis of overdose trends from 2005 to 2016 was based on naloxone distribution data from state Medicaid agencies and opioid-related mortality data from a national statistics system. Forty percent of nonelderly adults with an opioid addiction are covered by Medicaid, the researchers said.
They found that naloxone laws granting pharmacists direct dispensing authority were linked to a drop in opioid deaths that increased in magnitude over time, according to researchers. The mean number of opioid deaths dropped by 27% in the second year after adoption of direct authority laws, relative to opioid deaths in states with indirect access laws, while in subsequent years, deaths dropped by 34%.
Emergency department visits related to opioids increased by 15% in direct authority states 3 or more years after adoption, as compared to states that did not adopt direct authority laws. According to investigators, that translated into 15 additional opioid-related emergency department visits each month.
That increase suggests that, alongside direct dispensing laws, “useful interventions” and connections to treatment are needed for the emergency department, according to Dr. Abouk and colleagues.
“This is the location where such programs may be the most effective,” they said in their report.
Future research should be done to determine whether removing gatekeepers increases the value of naloxone distribution policies, they concluded in the report.
Dr. Abouk had no disclosures. Co-authors on the study reported funding and conflict of interest disclosures related to the National Institute on Drug Abuse and the Centers for Disease Control and Prevention.
SOURCE: Abouk R, et al. JAMA Intern Med. 2019 May 6. doi:10.1001/jamainternmed.2019.0272.
FROM JAMA Internal Medicine
Key clinical point: State laws granting pharmacists direct authority to dispense naloxone were linked to significant drops in opioid-related fatal overdoses.
Major finding: The mean number of opioid deaths dropped by 27% in the second year after adoption of direct authority laws relative to opioid deaths in states with indirect access laws, while in subsequent years, deaths dropped by 34%.
Study details: Analysis of naloxone distribution data and opioid-related mortality data from 2005 to 2016 for all 50 states and the District of Columbia.
Disclosures: Study authors reported funding and conflict of interest disclosures related to the National Institute on Drug Abuse and the Centers for Disease Control and Prevention.
Source: Abouk R, et al. JAMA Intern Med. 2019 May 6.
CSF and plasma biomarkers predict survival in sporadic Creutzfeldt-Jakob disease
, according to research published online ahead of print May 6 in JAMA Neurology. Levels of total tau in plasma and CSF are correlated, and plasma total tau is associated with survival time. These findings suggest that plasma total tau level could be a valid biomarker that guides clinical care for patients with sporadic Creutzfeldt-Jakob disease, said the investigators.
The accurate prediction of disease duration can assist clinicians and caregivers in clinical management, as well as influence the design of clinical trials. Previous studies have found that baseline protein levels in CSF and plasma are associated with disease duration in patients with sporadic Creutzfeldt-Jakob disease. To replicate these findings, Adam M. Staffaroni, PhD, of the department of neurology at the University of California, San Francisco, and colleagues conducted a longitudinal cohort study.
Evaluating fluid and nonfluid biomarkers
Dr. Staffaroni and colleagues recruited 193 participants with probable or definite sporadic Creutzfeldt-Jakob disease who had codon 129 genotyping and were referred to the UCSF Memory and Aging Center from March 2004 to January 2018. All participants underwent cognitive testing, informant measures, a neurologic examination, and CSF and blood sample collection. The researchers excluded from analysis five participants who had been placed on life-extending treatments. Participants were evaluated until death or censored at the time of statistical analysis.
Dr. Staffaroni and colleagues examined the following nonfluid biomarkers of survival: sex, age, codon 129 genotype, Barthel Index, and Medical Research Council (MRC) Prion Disease Rating Scale. In addition, they examined total tau level, phosphorylated tau level, total tau:phosphorylated tau ratio, neurofilament light (NfL) level, beta-amyloid 42 level, neuron-specific enolase level, 14-3-3 test result, and real-time quaking-induced conversion test in CSF as fluid biomarkers of survival. Finally, Dr. Staffaroni’s group analyzed total tau level, NfL level, and glial fibrillary acidic protein level in plasma as additional fluid biomarkers of survival.
The researchers fitted Cox proportional hazard models with time to event as the outcome. They log-transformed fluid biomarkers and ran models with and without nonfluid biomarkers of survival.
Plasma total tau was associated with survival
In all, 188 patients were included in the analysis. The population’s mean age was 63.8 years. Approximately 45% of participants were women. The diagnosis of sporadic Creutzfeldt-Jakob disease was pathologically confirmed for 78.2% of participants and probable for 21.8% of participants.
Dr. Staffaroni’s group observed strong correlations between plasma and CSF NfL concentrations and between plasma and CSF total tau concentrations. CSF total tau and CSF NfL concentrations were also correlated.
Among the nonfluid biomarkers, Barthel Index, MRC Scale, and codon 129 genotype were significantly associated with survival time. Lower level of function at baseline predicted a faster disease course.
Among the fluid biomarkers, greater levels of plasma total tau and NfL levels at baseline were associated with shorter survival. After the investigators controlled for Barthel Index and codon 129 genotype, the association of plasma total tau level with survival time remained significant. Plasma total tau level and Barthel Index (hazard ratio, 0.98) each independently predicted survival. Dr. Staffaroni and colleagues found that the hazard ratios for all CSF biomarkers were in the expected direction, and that those for total tau level, total tau:phosphorylated tau ratio, NfL level, and neuron-specific enolase level were statistically significant. Furthermore, positive results for 14-3-3 protein, neuron-specific enolase level, and total tau level were associated with a shorter time until death. Like the plasma biomarkers, CSF total tau level remained associated with survival after the investigators controlled for Barthel Index and codon 129 genotype. The same was true of CSF total tau:phosphorylated tau ratio, neuron-specific enolase level, and 14-3-3 result.
Plasma tau could be a diagnostic biomarker
“The hazard ratio associated with plasma total tau level was more than 40% higher than other fluid biomarkers of interest,” said the authors. “These findings further bolster the value of blood-based biomarkers, based on their minimally invasive and relatively inexpensive nature, and build on prior studies that suggested patients with sporadic Creutzfeldt-Jakob disease and controls can be discriminated with relatively high accuracy using blood-based assays.” When Dr. Staffaroni and colleagues modeled baseline functional status and plasma total tau levels together, they found that both were independent predictors of survival time. “This [finding] suggests that clinical measures and plasma total tau level could be combined to further improve prediction accuracy.”
Among the study’s limitations was its comparatively small subsample of patients for whom all plasma and CSF biomarkers were available. Disease duration and survival were longer in the study population than in the literature. “Another limitation is that the plasma biomarkers in this study, one of which showed great promise for predicting survival, were assayed using a research protocol,” said the researchers. “Widespread clinical use of these biomarkers will require well-validated commercial assays, development of which is underway.”
Before these biomarkers can be used in the clinic, these results will need to be replicated, and neurologists will need to develop consensus cutoffs for the biomarker levels. The researchers did not analyze plasma tau level as a diagnostic biomarker, but future studies should examine this potential, Dr. Staffaroni and colleagues concluded.
Grants from the National Institute on Aging and the National Institute of Allergy and Infectious Diseases supported the study.
SOURCE: Staffaroni AM et al. JAMA Neurol. 2019 May 6. doi: 10.1001/jamaneurol.2019.1071.
, according to research published online ahead of print May 6 in JAMA Neurology. Levels of total tau in plasma and CSF are correlated, and plasma total tau is associated with survival time. These findings suggest that plasma total tau level could be a valid biomarker that guides clinical care for patients with sporadic Creutzfeldt-Jakob disease, said the investigators.
The accurate prediction of disease duration can assist clinicians and caregivers in clinical management, as well as influence the design of clinical trials. Previous studies have found that baseline protein levels in CSF and plasma are associated with disease duration in patients with sporadic Creutzfeldt-Jakob disease. To replicate these findings, Adam M. Staffaroni, PhD, of the department of neurology at the University of California, San Francisco, and colleagues conducted a longitudinal cohort study.
Evaluating fluid and nonfluid biomarkers
Dr. Staffaroni and colleagues recruited 193 participants with probable or definite sporadic Creutzfeldt-Jakob disease who had codon 129 genotyping and were referred to the UCSF Memory and Aging Center from March 2004 to January 2018. All participants underwent cognitive testing, informant measures, a neurologic examination, and CSF and blood sample collection. The researchers excluded from analysis five participants who had been placed on life-extending treatments. Participants were evaluated until death or censored at the time of statistical analysis.
Dr. Staffaroni and colleagues examined the following nonfluid biomarkers of survival: sex, age, codon 129 genotype, Barthel Index, and Medical Research Council (MRC) Prion Disease Rating Scale. In addition, they examined total tau level, phosphorylated tau level, total tau:phosphorylated tau ratio, neurofilament light (NfL) level, beta-amyloid 42 level, neuron-specific enolase level, 14-3-3 test result, and real-time quaking-induced conversion test in CSF as fluid biomarkers of survival. Finally, Dr. Staffaroni’s group analyzed total tau level, NfL level, and glial fibrillary acidic protein level in plasma as additional fluid biomarkers of survival.
The researchers fitted Cox proportional hazard models with time to event as the outcome. They log-transformed fluid biomarkers and ran models with and without nonfluid biomarkers of survival.
Plasma total tau was associated with survival
In all, 188 patients were included in the analysis. The population’s mean age was 63.8 years. Approximately 45% of participants were women. The diagnosis of sporadic Creutzfeldt-Jakob disease was pathologically confirmed for 78.2% of participants and probable for 21.8% of participants.
Dr. Staffaroni’s group observed strong correlations between plasma and CSF NfL concentrations and between plasma and CSF total tau concentrations. CSF total tau and CSF NfL concentrations were also correlated.
Among the nonfluid biomarkers, Barthel Index, MRC Scale, and codon 129 genotype were significantly associated with survival time. Lower level of function at baseline predicted a faster disease course.
Among the fluid biomarkers, greater levels of plasma total tau and NfL levels at baseline were associated with shorter survival. After the investigators controlled for Barthel Index and codon 129 genotype, the association of plasma total tau level with survival time remained significant. Plasma total tau level and Barthel Index (hazard ratio, 0.98) each independently predicted survival. Dr. Staffaroni and colleagues found that the hazard ratios for all CSF biomarkers were in the expected direction, and that those for total tau level, total tau:phosphorylated tau ratio, NfL level, and neuron-specific enolase level were statistically significant. Furthermore, positive results for 14-3-3 protein, neuron-specific enolase level, and total tau level were associated with a shorter time until death. Like the plasma biomarkers, CSF total tau level remained associated with survival after the investigators controlled for Barthel Index and codon 129 genotype. The same was true of CSF total tau:phosphorylated tau ratio, neuron-specific enolase level, and 14-3-3 result.
Plasma tau could be a diagnostic biomarker
“The hazard ratio associated with plasma total tau level was more than 40% higher than other fluid biomarkers of interest,” said the authors. “These findings further bolster the value of blood-based biomarkers, based on their minimally invasive and relatively inexpensive nature, and build on prior studies that suggested patients with sporadic Creutzfeldt-Jakob disease and controls can be discriminated with relatively high accuracy using blood-based assays.” When Dr. Staffaroni and colleagues modeled baseline functional status and plasma total tau levels together, they found that both were independent predictors of survival time. “This [finding] suggests that clinical measures and plasma total tau level could be combined to further improve prediction accuracy.”
Among the study’s limitations was its comparatively small subsample of patients for whom all plasma and CSF biomarkers were available. Disease duration and survival were longer in the study population than in the literature. “Another limitation is that the plasma biomarkers in this study, one of which showed great promise for predicting survival, were assayed using a research protocol,” said the researchers. “Widespread clinical use of these biomarkers will require well-validated commercial assays, development of which is underway.”
Before these biomarkers can be used in the clinic, these results will need to be replicated, and neurologists will need to develop consensus cutoffs for the biomarker levels. The researchers did not analyze plasma tau level as a diagnostic biomarker, but future studies should examine this potential, Dr. Staffaroni and colleagues concluded.
Grants from the National Institute on Aging and the National Institute of Allergy and Infectious Diseases supported the study.
SOURCE: Staffaroni AM et al. JAMA Neurol. 2019 May 6. doi: 10.1001/jamaneurol.2019.1071.
, according to research published online ahead of print May 6 in JAMA Neurology. Levels of total tau in plasma and CSF are correlated, and plasma total tau is associated with survival time. These findings suggest that plasma total tau level could be a valid biomarker that guides clinical care for patients with sporadic Creutzfeldt-Jakob disease, said the investigators.
The accurate prediction of disease duration can assist clinicians and caregivers in clinical management, as well as influence the design of clinical trials. Previous studies have found that baseline protein levels in CSF and plasma are associated with disease duration in patients with sporadic Creutzfeldt-Jakob disease. To replicate these findings, Adam M. Staffaroni, PhD, of the department of neurology at the University of California, San Francisco, and colleagues conducted a longitudinal cohort study.
Evaluating fluid and nonfluid biomarkers
Dr. Staffaroni and colleagues recruited 193 participants with probable or definite sporadic Creutzfeldt-Jakob disease who had codon 129 genotyping and were referred to the UCSF Memory and Aging Center from March 2004 to January 2018. All participants underwent cognitive testing, informant measures, a neurologic examination, and CSF and blood sample collection. The researchers excluded from analysis five participants who had been placed on life-extending treatments. Participants were evaluated until death or censored at the time of statistical analysis.
Dr. Staffaroni and colleagues examined the following nonfluid biomarkers of survival: sex, age, codon 129 genotype, Barthel Index, and Medical Research Council (MRC) Prion Disease Rating Scale. In addition, they examined total tau level, phosphorylated tau level, total tau:phosphorylated tau ratio, neurofilament light (NfL) level, beta-amyloid 42 level, neuron-specific enolase level, 14-3-3 test result, and real-time quaking-induced conversion test in CSF as fluid biomarkers of survival. Finally, Dr. Staffaroni’s group analyzed total tau level, NfL level, and glial fibrillary acidic protein level in plasma as additional fluid biomarkers of survival.
The researchers fitted Cox proportional hazard models with time to event as the outcome. They log-transformed fluid biomarkers and ran models with and without nonfluid biomarkers of survival.
Plasma total tau was associated with survival
In all, 188 patients were included in the analysis. The population’s mean age was 63.8 years. Approximately 45% of participants were women. The diagnosis of sporadic Creutzfeldt-Jakob disease was pathologically confirmed for 78.2% of participants and probable for 21.8% of participants.
Dr. Staffaroni’s group observed strong correlations between plasma and CSF NfL concentrations and between plasma and CSF total tau concentrations. CSF total tau and CSF NfL concentrations were also correlated.
Among the nonfluid biomarkers, Barthel Index, MRC Scale, and codon 129 genotype were significantly associated with survival time. Lower level of function at baseline predicted a faster disease course.
Among the fluid biomarkers, greater levels of plasma total tau and NfL levels at baseline were associated with shorter survival. After the investigators controlled for Barthel Index and codon 129 genotype, the association of plasma total tau level with survival time remained significant. Plasma total tau level and Barthel Index (hazard ratio, 0.98) each independently predicted survival. Dr. Staffaroni and colleagues found that the hazard ratios for all CSF biomarkers were in the expected direction, and that those for total tau level, total tau:phosphorylated tau ratio, NfL level, and neuron-specific enolase level were statistically significant. Furthermore, positive results for 14-3-3 protein, neuron-specific enolase level, and total tau level were associated with a shorter time until death. Like the plasma biomarkers, CSF total tau level remained associated with survival after the investigators controlled for Barthel Index and codon 129 genotype. The same was true of CSF total tau:phosphorylated tau ratio, neuron-specific enolase level, and 14-3-3 result.
Plasma tau could be a diagnostic biomarker
“The hazard ratio associated with plasma total tau level was more than 40% higher than other fluid biomarkers of interest,” said the authors. “These findings further bolster the value of blood-based biomarkers, based on their minimally invasive and relatively inexpensive nature, and build on prior studies that suggested patients with sporadic Creutzfeldt-Jakob disease and controls can be discriminated with relatively high accuracy using blood-based assays.” When Dr. Staffaroni and colleagues modeled baseline functional status and plasma total tau levels together, they found that both were independent predictors of survival time. “This [finding] suggests that clinical measures and plasma total tau level could be combined to further improve prediction accuracy.”
Among the study’s limitations was its comparatively small subsample of patients for whom all plasma and CSF biomarkers were available. Disease duration and survival were longer in the study population than in the literature. “Another limitation is that the plasma biomarkers in this study, one of which showed great promise for predicting survival, were assayed using a research protocol,” said the researchers. “Widespread clinical use of these biomarkers will require well-validated commercial assays, development of which is underway.”
Before these biomarkers can be used in the clinic, these results will need to be replicated, and neurologists will need to develop consensus cutoffs for the biomarker levels. The researchers did not analyze plasma tau level as a diagnostic biomarker, but future studies should examine this potential, Dr. Staffaroni and colleagues concluded.
Grants from the National Institute on Aging and the National Institute of Allergy and Infectious Diseases supported the study.
SOURCE: Staffaroni AM et al. JAMA Neurol. 2019 May 6. doi: 10.1001/jamaneurol.2019.1071.
FROM JAMA NEUROLOGY
Key clinical point: Invasive and minimally invasive biomarkers are associated with survival in sporadic Creutzfeldt-Jakob disease.
Major finding: The hazard ratio for plasma total tau level was more than 40% larger than any other biomarker.
Study details: A longitudinal study of 188 participants with sporadic Creutzfeldt-Jakob disease.
Disclosures: Grants from the National Institute on Aging and the National Institute of Allergy and Infectious Diseases supported the study.
Source: Staffaroni AM et al. JAMA Neurol. 2019 May 6. doi: 10.1001/jamaneurol.2019.1071.
How are US hospitals faring when it comes to implementing breastfeeding-friendly policies?
Endo fellows report lack of confidence in managing some after-hour calls
LOS ANGELES – When it comes to handling after-hours phone calls from patients, endocrinology fellows generally have less confidence in their decision making than their supervising faculty have in them, as measured by faculty’s reported agreement with fellows’ management plans. In addition, their confidence varies widely depending on the reason for call, results from a small, single-center study suggest.
“The research on training in telephone medicine is sparse,” lead study author Ramya Punati, MD, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “Our field relies on blood sugars and patient monitoring at home. We get a large volume of such calls, so while supervising faculty are always available for questions overnight, I think it would be useful to have a formal curriculum or feedback process in place at all major medical centers for fellows to learn how to appropriately manage outpatient calls.”
In October 2018, 6 endocrinology fellows and 13 endocrinology faculty members at the Hospital of the University of Pennsylvania, Philadelphia, completed baseline surveys. Fellows were asked how often they felt confident on after-hours calls managing specific conditions, such as problems with insulin pumps, positive ketones, and hyperglycemia and hypoglycemia. Faculty were asked how often they agreed with the fellows’ management of the same conditions.
One month later, the researchers implemented a two-part intervention. Part one consisted of a 1-hour didactic session for the six fellows about how to handle common outpatient diabetes-related calls. Part two involved a process by which faculty gave feedback through the EMR on decisions that fellows make on after-hours calls. Assistance provided in real time by supervising faculty was not measured.
In April 2019, the researchers used the same surveys to reassess the fellows’ and the faculty’s confidence. In addition, “pre- and postintervention, fellows were asked two questions to reflect on the perceived utility of taking outpatient calls,” said Dr. Punati, who is an endocrinology fellow at the Hospital of the University of Pennsylvania. “One was, ‘Do you feel that taking outpatient calls allows you to impact patient care in a meaningful way?’ The other was, ‘Do you feel that taking after-hours calls is educational for you?’ ”
At baseline, all fellows reported that they rarely received feedback from outpatient faculty on decisions they make on after-hours calls. Following implementation of the intervention, most fellows reported a slight increase in the feedback received. Pre- and postintervention, most fellows said that they were able to affect care in a meaningful way by handling after-hours calls, but felt that taking such calls had more limited educational value.
She and her colleagues found that faculty confidence in after-hour decision making by endocrine fellows is generally higher than fellows’ reported confidence in the same domains. At baseline, both faculty and fellows had highest confidence in the ability of fellows to manage calls related to fluctuations in blood glucose, and both groups had lowest ratings in management of insulin pump problems and diabetic ketoacidosis. After the intervention, both fellows and faculty had increased confidence in the ability of fellows to manage all types of calls, compared with baseline.
“It’s hard to say how much of the improvement is due to the intervention versus the passage of time and experience,” Dr. Punati said. “By the nature of taking more calls and getting more experience, fellows are going to get more confident as the year goes on.”
Fellows’ responses about their confidence in handling after-hours calls and their perception of the educational value of that responsibility highlight the need for a more formalized curriculum in telephone medicine and feedback process, she said.
Dr. Punati recommends a combination of didactic instruction early in endocrinology fellowship training and ongoing feedback for decisions that fellows make during after-hours calls.
“That process of feedback is the only way fellows will improve their knowledge and their confidence in handling these calls,” she said. In fact, as a result of the study, the university’s endocrinology fellowship program has already implemented changes in the academic curriculum to enhance the fellows’ educational experience and provide them with tools they need to confidently manage these calls.
Dr. Punati reported having no financial disclosures.
LOS ANGELES – When it comes to handling after-hours phone calls from patients, endocrinology fellows generally have less confidence in their decision making than their supervising faculty have in them, as measured by faculty’s reported agreement with fellows’ management plans. In addition, their confidence varies widely depending on the reason for call, results from a small, single-center study suggest.
“The research on training in telephone medicine is sparse,” lead study author Ramya Punati, MD, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “Our field relies on blood sugars and patient monitoring at home. We get a large volume of such calls, so while supervising faculty are always available for questions overnight, I think it would be useful to have a formal curriculum or feedback process in place at all major medical centers for fellows to learn how to appropriately manage outpatient calls.”
In October 2018, 6 endocrinology fellows and 13 endocrinology faculty members at the Hospital of the University of Pennsylvania, Philadelphia, completed baseline surveys. Fellows were asked how often they felt confident on after-hours calls managing specific conditions, such as problems with insulin pumps, positive ketones, and hyperglycemia and hypoglycemia. Faculty were asked how often they agreed with the fellows’ management of the same conditions.
One month later, the researchers implemented a two-part intervention. Part one consisted of a 1-hour didactic session for the six fellows about how to handle common outpatient diabetes-related calls. Part two involved a process by which faculty gave feedback through the EMR on decisions that fellows make on after-hours calls. Assistance provided in real time by supervising faculty was not measured.
In April 2019, the researchers used the same surveys to reassess the fellows’ and the faculty’s confidence. In addition, “pre- and postintervention, fellows were asked two questions to reflect on the perceived utility of taking outpatient calls,” said Dr. Punati, who is an endocrinology fellow at the Hospital of the University of Pennsylvania. “One was, ‘Do you feel that taking outpatient calls allows you to impact patient care in a meaningful way?’ The other was, ‘Do you feel that taking after-hours calls is educational for you?’ ”
At baseline, all fellows reported that they rarely received feedback from outpatient faculty on decisions they make on after-hours calls. Following implementation of the intervention, most fellows reported a slight increase in the feedback received. Pre- and postintervention, most fellows said that they were able to affect care in a meaningful way by handling after-hours calls, but felt that taking such calls had more limited educational value.
She and her colleagues found that faculty confidence in after-hour decision making by endocrine fellows is generally higher than fellows’ reported confidence in the same domains. At baseline, both faculty and fellows had highest confidence in the ability of fellows to manage calls related to fluctuations in blood glucose, and both groups had lowest ratings in management of insulin pump problems and diabetic ketoacidosis. After the intervention, both fellows and faculty had increased confidence in the ability of fellows to manage all types of calls, compared with baseline.
“It’s hard to say how much of the improvement is due to the intervention versus the passage of time and experience,” Dr. Punati said. “By the nature of taking more calls and getting more experience, fellows are going to get more confident as the year goes on.”
Fellows’ responses about their confidence in handling after-hours calls and their perception of the educational value of that responsibility highlight the need for a more formalized curriculum in telephone medicine and feedback process, she said.
Dr. Punati recommends a combination of didactic instruction early in endocrinology fellowship training and ongoing feedback for decisions that fellows make during after-hours calls.
“That process of feedback is the only way fellows will improve their knowledge and their confidence in handling these calls,” she said. In fact, as a result of the study, the university’s endocrinology fellowship program has already implemented changes in the academic curriculum to enhance the fellows’ educational experience and provide them with tools they need to confidently manage these calls.
Dr. Punati reported having no financial disclosures.
LOS ANGELES – When it comes to handling after-hours phone calls from patients, endocrinology fellows generally have less confidence in their decision making than their supervising faculty have in them, as measured by faculty’s reported agreement with fellows’ management plans. In addition, their confidence varies widely depending on the reason for call, results from a small, single-center study suggest.
“The research on training in telephone medicine is sparse,” lead study author Ramya Punati, MD, said in an interview in advance of the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “Our field relies on blood sugars and patient monitoring at home. We get a large volume of such calls, so while supervising faculty are always available for questions overnight, I think it would be useful to have a formal curriculum or feedback process in place at all major medical centers for fellows to learn how to appropriately manage outpatient calls.”
In October 2018, 6 endocrinology fellows and 13 endocrinology faculty members at the Hospital of the University of Pennsylvania, Philadelphia, completed baseline surveys. Fellows were asked how often they felt confident on after-hours calls managing specific conditions, such as problems with insulin pumps, positive ketones, and hyperglycemia and hypoglycemia. Faculty were asked how often they agreed with the fellows’ management of the same conditions.
One month later, the researchers implemented a two-part intervention. Part one consisted of a 1-hour didactic session for the six fellows about how to handle common outpatient diabetes-related calls. Part two involved a process by which faculty gave feedback through the EMR on decisions that fellows make on after-hours calls. Assistance provided in real time by supervising faculty was not measured.
In April 2019, the researchers used the same surveys to reassess the fellows’ and the faculty’s confidence. In addition, “pre- and postintervention, fellows were asked two questions to reflect on the perceived utility of taking outpatient calls,” said Dr. Punati, who is an endocrinology fellow at the Hospital of the University of Pennsylvania. “One was, ‘Do you feel that taking outpatient calls allows you to impact patient care in a meaningful way?’ The other was, ‘Do you feel that taking after-hours calls is educational for you?’ ”
At baseline, all fellows reported that they rarely received feedback from outpatient faculty on decisions they make on after-hours calls. Following implementation of the intervention, most fellows reported a slight increase in the feedback received. Pre- and postintervention, most fellows said that they were able to affect care in a meaningful way by handling after-hours calls, but felt that taking such calls had more limited educational value.
She and her colleagues found that faculty confidence in after-hour decision making by endocrine fellows is generally higher than fellows’ reported confidence in the same domains. At baseline, both faculty and fellows had highest confidence in the ability of fellows to manage calls related to fluctuations in blood glucose, and both groups had lowest ratings in management of insulin pump problems and diabetic ketoacidosis. After the intervention, both fellows and faculty had increased confidence in the ability of fellows to manage all types of calls, compared with baseline.
“It’s hard to say how much of the improvement is due to the intervention versus the passage of time and experience,” Dr. Punati said. “By the nature of taking more calls and getting more experience, fellows are going to get more confident as the year goes on.”
Fellows’ responses about their confidence in handling after-hours calls and their perception of the educational value of that responsibility highlight the need for a more formalized curriculum in telephone medicine and feedback process, she said.
Dr. Punati recommends a combination of didactic instruction early in endocrinology fellowship training and ongoing feedback for decisions that fellows make during after-hours calls.
“That process of feedback is the only way fellows will improve their knowledge and their confidence in handling these calls,” she said. In fact, as a result of the study, the university’s endocrinology fellowship program has already implemented changes in the academic curriculum to enhance the fellows’ educational experience and provide them with tools they need to confidently manage these calls.
Dr. Punati reported having no financial disclosures.
REPORTING FROM AACE 2019
Key clinical point:
Major finding: Before and after intervention, most fellows said that they were able to affect care in a meaningful way by handling after-hours calls, but felt that taking such calls had more limited educational value.
Study details: A survey of 6 endocrinology fellows and 13 endocrinology faculty members at the Hospital of the University of Pennsylvania, Philadelphia.
Disclosures: Dr. Punati reported having no financial disclosures.
New adventures of an old device: Clinic delivers cortisol via the insulin pump
LOS ANGELES – The venerable insulin pump is being repurposed: A Detroit-area endocrinology
“We’ve seen amazing results,” said endocrinologist Opada Alzohaili, MD, MBA, of Wayne State University, Detroit, coauthor of a study released at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists.
Dr. Alzohaili said he and his colleagues developed the approach to manage patients who are “so sick that they go to the hospital 10-12 times a year.” Oral medication just did not control their disorder.
“Most of the time, we end up way overdosing them [on oral medication] just to prevent them from going to the hospital in adrenal crisis,” he said in an interview.
Dr. Alzohaili said his clinic has tested delivering hydrocortisone via insulin pump in about 20 patients. The report presented at the conference focused on six patients who had failed oral hydrocortisone treatment for adrenal insufficiency. Testing showed that all had malabsorption of the drug.
The patients underwent training in how to use and adjust the pump, which allows dosing adjustments in increments of 1 mg. They learned how to adjust their doses based on their situation, Dr. Alzohaili said.
According to the report, the average number of adrenal crises in the patients over a 6-month period fell from a mean of 2.3 before baseline to 0.5 after treatment began. The maximum dose of hydrocortisone dose fell by 38%, while the average mean weight of patients rose from 182 pounds to 199 pounds.
In addition, the mean dose of hydrocortisone decreased with the use of the pump delivery system, from 85.8 mg with oral treatment to 32.4 mg on pump therapy, and the mean level of cortisol increased from 11.8 mcg/dL with oral treatment to 12.3 mcg/dL on pump therapy.
The researchers said that the pump provides better delivery of the medication compared with the oral route, and that the patients experienced fewer interactions with other medications.
Some patients developed skin reactions to the pump, but those adverse events were resolved by changing the pump’s location on the body and by using hypoallergenic needles, Dr. Alzohaili said.
There were fewer cases of clogging with the pumps than is normally seen when they’re used with insulin, he added.
As for expense, Dr. Alzohaili said the pumps cost thousands of dollars and supplies can cost between $100 and $150 a month. In the first couple of cases, patients paid for the treatment themselves, he said, but in later cases, insurers were willing to pay for the treatment once they learned about the results.
Other researchers have successfully used insulin pumps to deliver hydrocortisone to small numbers of patients with adrenal insufficiency, including British and U.S. teams that reported positive results in 2015 and 2018, respectively.
The next step, Dr. Alzohaili said, is to attract the interest of insulin pump manufacturers by using the treatment in more patients. “I’ve spoken to CEOs, but none of them is interested in using cortisol in their pumps,” he said. “If you don’t have the company supporting the research, it becomes difficult for it to become standard of care. So I’m trying to build awareness [of its use] and the number of patients [who use the pump].”
Dr. Alzohaili reported no financial conflicts of interest or disclosures.
LOS ANGELES – The venerable insulin pump is being repurposed: A Detroit-area endocrinology
“We’ve seen amazing results,” said endocrinologist Opada Alzohaili, MD, MBA, of Wayne State University, Detroit, coauthor of a study released at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists.
Dr. Alzohaili said he and his colleagues developed the approach to manage patients who are “so sick that they go to the hospital 10-12 times a year.” Oral medication just did not control their disorder.
“Most of the time, we end up way overdosing them [on oral medication] just to prevent them from going to the hospital in adrenal crisis,” he said in an interview.
Dr. Alzohaili said his clinic has tested delivering hydrocortisone via insulin pump in about 20 patients. The report presented at the conference focused on six patients who had failed oral hydrocortisone treatment for adrenal insufficiency. Testing showed that all had malabsorption of the drug.
The patients underwent training in how to use and adjust the pump, which allows dosing adjustments in increments of 1 mg. They learned how to adjust their doses based on their situation, Dr. Alzohaili said.
According to the report, the average number of adrenal crises in the patients over a 6-month period fell from a mean of 2.3 before baseline to 0.5 after treatment began. The maximum dose of hydrocortisone dose fell by 38%, while the average mean weight of patients rose from 182 pounds to 199 pounds.
In addition, the mean dose of hydrocortisone decreased with the use of the pump delivery system, from 85.8 mg with oral treatment to 32.4 mg on pump therapy, and the mean level of cortisol increased from 11.8 mcg/dL with oral treatment to 12.3 mcg/dL on pump therapy.
The researchers said that the pump provides better delivery of the medication compared with the oral route, and that the patients experienced fewer interactions with other medications.
Some patients developed skin reactions to the pump, but those adverse events were resolved by changing the pump’s location on the body and by using hypoallergenic needles, Dr. Alzohaili said.
There were fewer cases of clogging with the pumps than is normally seen when they’re used with insulin, he added.
As for expense, Dr. Alzohaili said the pumps cost thousands of dollars and supplies can cost between $100 and $150 a month. In the first couple of cases, patients paid for the treatment themselves, he said, but in later cases, insurers were willing to pay for the treatment once they learned about the results.
Other researchers have successfully used insulin pumps to deliver hydrocortisone to small numbers of patients with adrenal insufficiency, including British and U.S. teams that reported positive results in 2015 and 2018, respectively.
The next step, Dr. Alzohaili said, is to attract the interest of insulin pump manufacturers by using the treatment in more patients. “I’ve spoken to CEOs, but none of them is interested in using cortisol in their pumps,” he said. “If you don’t have the company supporting the research, it becomes difficult for it to become standard of care. So I’m trying to build awareness [of its use] and the number of patients [who use the pump].”
Dr. Alzohaili reported no financial conflicts of interest or disclosures.
LOS ANGELES – The venerable insulin pump is being repurposed: A Detroit-area endocrinology
“We’ve seen amazing results,” said endocrinologist Opada Alzohaili, MD, MBA, of Wayne State University, Detroit, coauthor of a study released at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists.
Dr. Alzohaili said he and his colleagues developed the approach to manage patients who are “so sick that they go to the hospital 10-12 times a year.” Oral medication just did not control their disorder.
“Most of the time, we end up way overdosing them [on oral medication] just to prevent them from going to the hospital in adrenal crisis,” he said in an interview.
Dr. Alzohaili said his clinic has tested delivering hydrocortisone via insulin pump in about 20 patients. The report presented at the conference focused on six patients who had failed oral hydrocortisone treatment for adrenal insufficiency. Testing showed that all had malabsorption of the drug.
The patients underwent training in how to use and adjust the pump, which allows dosing adjustments in increments of 1 mg. They learned how to adjust their doses based on their situation, Dr. Alzohaili said.
According to the report, the average number of adrenal crises in the patients over a 6-month period fell from a mean of 2.3 before baseline to 0.5 after treatment began. The maximum dose of hydrocortisone dose fell by 38%, while the average mean weight of patients rose from 182 pounds to 199 pounds.
In addition, the mean dose of hydrocortisone decreased with the use of the pump delivery system, from 85.8 mg with oral treatment to 32.4 mg on pump therapy, and the mean level of cortisol increased from 11.8 mcg/dL with oral treatment to 12.3 mcg/dL on pump therapy.
The researchers said that the pump provides better delivery of the medication compared with the oral route, and that the patients experienced fewer interactions with other medications.
Some patients developed skin reactions to the pump, but those adverse events were resolved by changing the pump’s location on the body and by using hypoallergenic needles, Dr. Alzohaili said.
There were fewer cases of clogging with the pumps than is normally seen when they’re used with insulin, he added.
As for expense, Dr. Alzohaili said the pumps cost thousands of dollars and supplies can cost between $100 and $150 a month. In the first couple of cases, patients paid for the treatment themselves, he said, but in later cases, insurers were willing to pay for the treatment once they learned about the results.
Other researchers have successfully used insulin pumps to deliver hydrocortisone to small numbers of patients with adrenal insufficiency, including British and U.S. teams that reported positive results in 2015 and 2018, respectively.
The next step, Dr. Alzohaili said, is to attract the interest of insulin pump manufacturers by using the treatment in more patients. “I’ve spoken to CEOs, but none of them is interested in using cortisol in their pumps,” he said. “If you don’t have the company supporting the research, it becomes difficult for it to become standard of care. So I’m trying to build awareness [of its use] and the number of patients [who use the pump].”
Dr. Alzohaili reported no financial conflicts of interest or disclosures.
REPORTING FROM AACE 2019
FDA approves T-DM1 as adjuvant treatment
The Food and Drug Administration has approved the antibody-drug conjugate trastuzumab emtansine (T-DM1) for adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant treatment with a taxane and trastuzumab (Herceptin).
Approval of adjuvant T-DM1, marketed as Kadcyla, was based on a reduced risk of breast cancer recurrence or death in the phase 3 KATHERINE trial. In KATHERINE, over 1,400 patients with HER2-positive early breast cancer who had residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment were randomized to adjuvant therapy with T-DM1 or trastuzumab. The 3-year invasive disease-free survival rate was 88.3% for those taking T-DM1, compared with 77.0% for patients assigned to adjuvant trastuzumab (hazard ratio, 0.50; 95% confidence interval, 0.39-0.64; P less than .0001). Results of KATHERINE were presented at the 2018 San Antonio Breast Cancer Symposium and simultaneously published in the New England Journal of Medicine.
The most common grade 3 or greater adverse events for those in the T-DM1 arm included decreased platelet count in 5.7% and hypertension in 2.0%. The most common side effects with T-DM1 were fatigue, nausea, increased blood levels of liver enzymes, musculoskeletal pain, bleeding, decreased platelet count, headache, numbness in the hands or feet, and joint pain.
T-DM1 was previously approved to treat metastatic HER2-positive breast cancer after prior treatment with trastuzumab and a taxane.
“This approval is a significant treatment advance for HER2-positive early breast cancer. By working closely with the FDA and participating in the Real-Time Oncology Review pilot program, we are able to make Kadcyla available for people with residual invasive disease after neoadjuvant therapy much sooner than anticipated,” said Sandra Horning, MD, chief medical officer and head of global product development at Genentech (Roche), the developer of T-DM1, in a press release announcing the current approval.
The Food and Drug Administration has approved the antibody-drug conjugate trastuzumab emtansine (T-DM1) for adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant treatment with a taxane and trastuzumab (Herceptin).
Approval of adjuvant T-DM1, marketed as Kadcyla, was based on a reduced risk of breast cancer recurrence or death in the phase 3 KATHERINE trial. In KATHERINE, over 1,400 patients with HER2-positive early breast cancer who had residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment were randomized to adjuvant therapy with T-DM1 or trastuzumab. The 3-year invasive disease-free survival rate was 88.3% for those taking T-DM1, compared with 77.0% for patients assigned to adjuvant trastuzumab (hazard ratio, 0.50; 95% confidence interval, 0.39-0.64; P less than .0001). Results of KATHERINE were presented at the 2018 San Antonio Breast Cancer Symposium and simultaneously published in the New England Journal of Medicine.
The most common grade 3 or greater adverse events for those in the T-DM1 arm included decreased platelet count in 5.7% and hypertension in 2.0%. The most common side effects with T-DM1 were fatigue, nausea, increased blood levels of liver enzymes, musculoskeletal pain, bleeding, decreased platelet count, headache, numbness in the hands or feet, and joint pain.
T-DM1 was previously approved to treat metastatic HER2-positive breast cancer after prior treatment with trastuzumab and a taxane.
“This approval is a significant treatment advance for HER2-positive early breast cancer. By working closely with the FDA and participating in the Real-Time Oncology Review pilot program, we are able to make Kadcyla available for people with residual invasive disease after neoadjuvant therapy much sooner than anticipated,” said Sandra Horning, MD, chief medical officer and head of global product development at Genentech (Roche), the developer of T-DM1, in a press release announcing the current approval.
The Food and Drug Administration has approved the antibody-drug conjugate trastuzumab emtansine (T-DM1) for adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant treatment with a taxane and trastuzumab (Herceptin).
Approval of adjuvant T-DM1, marketed as Kadcyla, was based on a reduced risk of breast cancer recurrence or death in the phase 3 KATHERINE trial. In KATHERINE, over 1,400 patients with HER2-positive early breast cancer who had residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment were randomized to adjuvant therapy with T-DM1 or trastuzumab. The 3-year invasive disease-free survival rate was 88.3% for those taking T-DM1, compared with 77.0% for patients assigned to adjuvant trastuzumab (hazard ratio, 0.50; 95% confidence interval, 0.39-0.64; P less than .0001). Results of KATHERINE were presented at the 2018 San Antonio Breast Cancer Symposium and simultaneously published in the New England Journal of Medicine.
The most common grade 3 or greater adverse events for those in the T-DM1 arm included decreased platelet count in 5.7% and hypertension in 2.0%. The most common side effects with T-DM1 were fatigue, nausea, increased blood levels of liver enzymes, musculoskeletal pain, bleeding, decreased platelet count, headache, numbness in the hands or feet, and joint pain.
T-DM1 was previously approved to treat metastatic HER2-positive breast cancer after prior treatment with trastuzumab and a taxane.
“This approval is a significant treatment advance for HER2-positive early breast cancer. By working closely with the FDA and participating in the Real-Time Oncology Review pilot program, we are able to make Kadcyla available for people with residual invasive disease after neoadjuvant therapy much sooner than anticipated,” said Sandra Horning, MD, chief medical officer and head of global product development at Genentech (Roche), the developer of T-DM1, in a press release announcing the current approval.
Restroom, locker room restrictions foster abuse of transgender teens
Transgender youth with restricted restroom and locker room use at school were significantly more likely to experience sexual assault at school than those without such restrictions, based on surveys from more than 3,000 teens in the United States who identified as transgender or nonbinary.
“Little is known about risk factors for sexual assault in gender minority adolescents, but school policies and practices play an important role in other forms of victimization,” including restricting transgender students from using restrooms or locker rooms that match their gender identities, wrote Gabriel R. Murchison, MPH, of Harvard University, Boston, Mass., and colleagues in Pediatrics (2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902).
To examine the relationship between school restroom/locker room policies and sexual assault on transgender teens, the researchers reviewed data from the Lesbian, Gay, Bisexual, Transgender, and Queer or Questioning (LGBTQ) Teen Study, an anonymous web-based survey of U.S. adolescents aged 13 to 17 years who could read and write in English. Participants were assigned to one of four gender groups: trans male, trans female, nonbinary who were assigned male at birth (AMAB), or nonbinary who were assigned female at birth (AFAB) based on the survey questions asking their sex assigned at birth and current gender identity. The final study population of 3,673 individuals included 1,359 boys and 1,947 nonbinary youth AFAB and 158 transgender girls and 209 nonbinary youth AMAB. The results were published in Pediatrics.
with risk ratios of 1.26 for transgender boys and 2.49 for transgender girls, and 1.42 for nonbinary AFAB youth. Restroom/locker room restrictions were not significantly associated with sexual abuse in nonbinary AMAB youth.
The 12-month prevalence of sexual assault was highest among nonbinary youth AFAB (27%), followed by 26.5% among transgender boys, 18.5% among transgender girls, and 17.6% among nonbinary youth AMAB.
Sexual assault was determined based on participants’ response to the question, “During the past 12 months, how many times did anyone force you to do sexual things that you did not want to do? (Count such things as kissing, touching, or being physically forced to have sexual intercourse.)” The researchers adjusted for multiple factors associated with adolescent sexual assault including alcohol use, family connectedness, and educational attainment of caregivers; as well as variables including exposure to antitransgender stigma and perception of teacher support at school.
The researchers also identified four mediating variables: sexual harassment, feeling safe in restrooms and locker rooms, feeling safe in other locations at school, and classmates’ knowledge of gender status.
“Significant indirect effects were present for all 4 mediating variables,” which included feel safe in restrooms and locker rooms, feel safe elsewhere in school, classmates know gender minority status, and sexual harassment. The fourth mediating variable mentioned fully explains “the association between restroom and locker room restrictions and sexual assault victimization,” the researchers wrote.
The findings were limited by several factors including the lack of racial diversity and the reliance on cross-sectional, nonprobability data, the researchers said.
However, the results are strengthened by the large sample size and suggest that avoiding restrictive policies at school can make a difference in reducing abuse of transgender teens, they wrote.
“From a prevention perspective, pediatricians are key advocates for transgender and nonbinary patients, and their role may include educating school officials and submitting letters confirming the patient’s need to express their gender identity,” that emphasize the importance of “safe, identity-congruent restrooms and locker rooms,” the researchers concluded.
The study was supported in part by the Office of Vice President for Research at the University of Connecticut, and the Human Rights Campaign Foundation provided in-kind support for the LGBTQ Teen Study. Mr. Murchison disclosed participation in survey development and data collection for the LGBTQ Teen Study as an employee of the Human Rights Campaign Foundation.
SOURCE: Murchison G et al. Pediatrics . 2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902 .
The study findings “make a compelling case for what we as gender specialist providers witness every day in our work: failure to support transgender and gender-expansive youth in being able to fully live in their affirmed gender puts them at physical as well as psychological risk,” wrote Diane Ehrensaft, PhD, and Stephen M. Rosenthal, MD, in an accompanying editorial.
What can reduce the risk of these youth experiencing abuse and assault, according to the editorialists, is putting policies in place that support them. Dr. Ehrensaft and Dr. Rosenthal cited the state of California’s 2013 decision to allow all students in public schools, from kindergarten through 12th grade “the right to use the bathroom and locker room consistent with their affirmed gender identity” as an example of something pediatricians should be advocating for in other states.
Restrictions on bathroom use to their assigned birth identity may cause transgender youth to be at increased risk for verbal and physical harassment and abuse, they said. It may also lead some to avoid restroom use and increase their risk for urinary tract infections, impacted stool, and school avoidance, the editorialists noted. They added that “[such] policies are often fear based, with nontransgender students thought to be the ones at risk for sexual assault by transgender intruders, by anyone whose genitalia does not match the one associated with the sign on the door, or by predators posing as transgender students.” The editorialists noted that these attitudes can come from school personnel or parents and that pediatricians should be aware of “the high prevalence of sexual assault” on transgender and gender nonbinary youth” (Pediatrics. 2019 May 6. doi: 10.1542/peds.2019-0554).
Dr. Ehrensaft and Dr. Rosenthal are affiliated with the Benioff Children’s Hospital at the University of California, San Francisco. They had no financial conflicts to disclose.
The study findings “make a compelling case for what we as gender specialist providers witness every day in our work: failure to support transgender and gender-expansive youth in being able to fully live in their affirmed gender puts them at physical as well as psychological risk,” wrote Diane Ehrensaft, PhD, and Stephen M. Rosenthal, MD, in an accompanying editorial.
What can reduce the risk of these youth experiencing abuse and assault, according to the editorialists, is putting policies in place that support them. Dr. Ehrensaft and Dr. Rosenthal cited the state of California’s 2013 decision to allow all students in public schools, from kindergarten through 12th grade “the right to use the bathroom and locker room consistent with their affirmed gender identity” as an example of something pediatricians should be advocating for in other states.
Restrictions on bathroom use to their assigned birth identity may cause transgender youth to be at increased risk for verbal and physical harassment and abuse, they said. It may also lead some to avoid restroom use and increase their risk for urinary tract infections, impacted stool, and school avoidance, the editorialists noted. They added that “[such] policies are often fear based, with nontransgender students thought to be the ones at risk for sexual assault by transgender intruders, by anyone whose genitalia does not match the one associated with the sign on the door, or by predators posing as transgender students.” The editorialists noted that these attitudes can come from school personnel or parents and that pediatricians should be aware of “the high prevalence of sexual assault” on transgender and gender nonbinary youth” (Pediatrics. 2019 May 6. doi: 10.1542/peds.2019-0554).
Dr. Ehrensaft and Dr. Rosenthal are affiliated with the Benioff Children’s Hospital at the University of California, San Francisco. They had no financial conflicts to disclose.
The study findings “make a compelling case for what we as gender specialist providers witness every day in our work: failure to support transgender and gender-expansive youth in being able to fully live in their affirmed gender puts them at physical as well as psychological risk,” wrote Diane Ehrensaft, PhD, and Stephen M. Rosenthal, MD, in an accompanying editorial.
What can reduce the risk of these youth experiencing abuse and assault, according to the editorialists, is putting policies in place that support them. Dr. Ehrensaft and Dr. Rosenthal cited the state of California’s 2013 decision to allow all students in public schools, from kindergarten through 12th grade “the right to use the bathroom and locker room consistent with their affirmed gender identity” as an example of something pediatricians should be advocating for in other states.
Restrictions on bathroom use to their assigned birth identity may cause transgender youth to be at increased risk for verbal and physical harassment and abuse, they said. It may also lead some to avoid restroom use and increase their risk for urinary tract infections, impacted stool, and school avoidance, the editorialists noted. They added that “[such] policies are often fear based, with nontransgender students thought to be the ones at risk for sexual assault by transgender intruders, by anyone whose genitalia does not match the one associated with the sign on the door, or by predators posing as transgender students.” The editorialists noted that these attitudes can come from school personnel or parents and that pediatricians should be aware of “the high prevalence of sexual assault” on transgender and gender nonbinary youth” (Pediatrics. 2019 May 6. doi: 10.1542/peds.2019-0554).
Dr. Ehrensaft and Dr. Rosenthal are affiliated with the Benioff Children’s Hospital at the University of California, San Francisco. They had no financial conflicts to disclose.
Transgender youth with restricted restroom and locker room use at school were significantly more likely to experience sexual assault at school than those without such restrictions, based on surveys from more than 3,000 teens in the United States who identified as transgender or nonbinary.
“Little is known about risk factors for sexual assault in gender minority adolescents, but school policies and practices play an important role in other forms of victimization,” including restricting transgender students from using restrooms or locker rooms that match their gender identities, wrote Gabriel R. Murchison, MPH, of Harvard University, Boston, Mass., and colleagues in Pediatrics (2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902).
To examine the relationship between school restroom/locker room policies and sexual assault on transgender teens, the researchers reviewed data from the Lesbian, Gay, Bisexual, Transgender, and Queer or Questioning (LGBTQ) Teen Study, an anonymous web-based survey of U.S. adolescents aged 13 to 17 years who could read and write in English. Participants were assigned to one of four gender groups: trans male, trans female, nonbinary who were assigned male at birth (AMAB), or nonbinary who were assigned female at birth (AFAB) based on the survey questions asking their sex assigned at birth and current gender identity. The final study population of 3,673 individuals included 1,359 boys and 1,947 nonbinary youth AFAB and 158 transgender girls and 209 nonbinary youth AMAB. The results were published in Pediatrics.
with risk ratios of 1.26 for transgender boys and 2.49 for transgender girls, and 1.42 for nonbinary AFAB youth. Restroom/locker room restrictions were not significantly associated with sexual abuse in nonbinary AMAB youth.
The 12-month prevalence of sexual assault was highest among nonbinary youth AFAB (27%), followed by 26.5% among transgender boys, 18.5% among transgender girls, and 17.6% among nonbinary youth AMAB.
Sexual assault was determined based on participants’ response to the question, “During the past 12 months, how many times did anyone force you to do sexual things that you did not want to do? (Count such things as kissing, touching, or being physically forced to have sexual intercourse.)” The researchers adjusted for multiple factors associated with adolescent sexual assault including alcohol use, family connectedness, and educational attainment of caregivers; as well as variables including exposure to antitransgender stigma and perception of teacher support at school.
The researchers also identified four mediating variables: sexual harassment, feeling safe in restrooms and locker rooms, feeling safe in other locations at school, and classmates’ knowledge of gender status.
“Significant indirect effects were present for all 4 mediating variables,” which included feel safe in restrooms and locker rooms, feel safe elsewhere in school, classmates know gender minority status, and sexual harassment. The fourth mediating variable mentioned fully explains “the association between restroom and locker room restrictions and sexual assault victimization,” the researchers wrote.
The findings were limited by several factors including the lack of racial diversity and the reliance on cross-sectional, nonprobability data, the researchers said.
However, the results are strengthened by the large sample size and suggest that avoiding restrictive policies at school can make a difference in reducing abuse of transgender teens, they wrote.
“From a prevention perspective, pediatricians are key advocates for transgender and nonbinary patients, and their role may include educating school officials and submitting letters confirming the patient’s need to express their gender identity,” that emphasize the importance of “safe, identity-congruent restrooms and locker rooms,” the researchers concluded.
The study was supported in part by the Office of Vice President for Research at the University of Connecticut, and the Human Rights Campaign Foundation provided in-kind support for the LGBTQ Teen Study. Mr. Murchison disclosed participation in survey development and data collection for the LGBTQ Teen Study as an employee of the Human Rights Campaign Foundation.
SOURCE: Murchison G et al. Pediatrics . 2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902 .
Transgender youth with restricted restroom and locker room use at school were significantly more likely to experience sexual assault at school than those without such restrictions, based on surveys from more than 3,000 teens in the United States who identified as transgender or nonbinary.
“Little is known about risk factors for sexual assault in gender minority adolescents, but school policies and practices play an important role in other forms of victimization,” including restricting transgender students from using restrooms or locker rooms that match their gender identities, wrote Gabriel R. Murchison, MPH, of Harvard University, Boston, Mass., and colleagues in Pediatrics (2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902).
To examine the relationship between school restroom/locker room policies and sexual assault on transgender teens, the researchers reviewed data from the Lesbian, Gay, Bisexual, Transgender, and Queer or Questioning (LGBTQ) Teen Study, an anonymous web-based survey of U.S. adolescents aged 13 to 17 years who could read and write in English. Participants were assigned to one of four gender groups: trans male, trans female, nonbinary who were assigned male at birth (AMAB), or nonbinary who were assigned female at birth (AFAB) based on the survey questions asking their sex assigned at birth and current gender identity. The final study population of 3,673 individuals included 1,359 boys and 1,947 nonbinary youth AFAB and 158 transgender girls and 209 nonbinary youth AMAB. The results were published in Pediatrics.
with risk ratios of 1.26 for transgender boys and 2.49 for transgender girls, and 1.42 for nonbinary AFAB youth. Restroom/locker room restrictions were not significantly associated with sexual abuse in nonbinary AMAB youth.
The 12-month prevalence of sexual assault was highest among nonbinary youth AFAB (27%), followed by 26.5% among transgender boys, 18.5% among transgender girls, and 17.6% among nonbinary youth AMAB.
Sexual assault was determined based on participants’ response to the question, “During the past 12 months, how many times did anyone force you to do sexual things that you did not want to do? (Count such things as kissing, touching, or being physically forced to have sexual intercourse.)” The researchers adjusted for multiple factors associated with adolescent sexual assault including alcohol use, family connectedness, and educational attainment of caregivers; as well as variables including exposure to antitransgender stigma and perception of teacher support at school.
The researchers also identified four mediating variables: sexual harassment, feeling safe in restrooms and locker rooms, feeling safe in other locations at school, and classmates’ knowledge of gender status.
“Significant indirect effects were present for all 4 mediating variables,” which included feel safe in restrooms and locker rooms, feel safe elsewhere in school, classmates know gender minority status, and sexual harassment. The fourth mediating variable mentioned fully explains “the association between restroom and locker room restrictions and sexual assault victimization,” the researchers wrote.
The findings were limited by several factors including the lack of racial diversity and the reliance on cross-sectional, nonprobability data, the researchers said.
However, the results are strengthened by the large sample size and suggest that avoiding restrictive policies at school can make a difference in reducing abuse of transgender teens, they wrote.
“From a prevention perspective, pediatricians are key advocates for transgender and nonbinary patients, and their role may include educating school officials and submitting letters confirming the patient’s need to express their gender identity,” that emphasize the importance of “safe, identity-congruent restrooms and locker rooms,” the researchers concluded.
The study was supported in part by the Office of Vice President for Research at the University of Connecticut, and the Human Rights Campaign Foundation provided in-kind support for the LGBTQ Teen Study. Mr. Murchison disclosed participation in survey development and data collection for the LGBTQ Teen Study as an employee of the Human Rights Campaign Foundation.
SOURCE: Murchison G et al. Pediatrics . 2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902 .
FROM PEDIATRICS
Key clinical point: Restrictive restroom and locker room environments in schools promote abuse of transgender teens.
Major finding: Sexual assault was significantly more likely against transgender teens with restroom and locker room restrictions vs those without restrictions, with risk ratios of 1.26 for transgender boys and 2.49 for transgender girls.
Study details: The data came from web-based surveys of 3,673 teens aged 13 to 17 years who identified as transgender or nonbinary.
Disclosures: The study was supported in part by the Office of Vice President for Research at the University of Connecticut, and the Human Rights Campaign Foundation provided in-kind support for the LGBTQ Teen Study. Mr. Murchison disclosed participation in survey development and data collection for the LGBTQ Teen Study as an employee of the Human Rights Campaign Foundation.
Source: Murchison G et al. Pediatrics. 2019 May 6. doi: https://doi.org/10.1542/peds.2018-2902
