User login
Neonatal epileptic syndromes are surprisingly common
BANGKOK – Katherine B. Howell, MD, reported at the International Epilepsy Congress.
“This is an important finding. It’s a considerably larger number than might have been expected and likely has two contributing factors. Neonatal seizures were previously not considered epilepsy, so many previous studies excluded neonates and the conditions were underrecognized. And our large number of ictal EEGs allowed identification of ictal activation, which is a feature of EIMFS [epilepsy of infancy with migrating focal seizures]. Without those ictal recordings, the diagnosis of EIMFS may not have been made,” according to Dr. Howell, a neurologist at the Royal Children’s Hospital and University of Melbourne.
She presented a population-based study of all infants born with severe epilepsies of infancy (SEI) during a 2-year period in the Australian state of Victoria, which is considered an ideal environment for epidemiologic studies because government-funded health care is available to all. SEI was defined as seizures beginning before age 18 months, occurring at a rate of at least one per day for 1 week or weekly for 1 month, refractory to adequate trials of at least two antiepileptic drugs, and accompanied by an epileptiform EEG abnormality. Her focus was on the electroclinical phenotypes of the affected children because of the high clinical utility of this information.
“Assigning an epileptic syndrome is highly useful for clinician-to-clinician communication of an infant’s phenotype. It guides investigation of etiology and possibly selection of optimal therapy, such as steroids in West syndrome. And it can inform prognosis,” Dr. Howell said at the congress sponsored by the International League Against Epilepsy.
She and her coinvestigators analyzed the detailed records of all 114 infants with SEI born during the study period. The incidence was 1 in 2,000 live births.
“Among infants with epilepsy, this patient group with SEI is most critical to better understand. Effective treatment is often not available, the seizure and developmental outcomes are frequently devastating, and the health burden massive,” the neurologist observed.
The full spectrum of SEI
With the help of ictal EEGs, home seizure recordings, MRI scans, and genomic testing, the investigators were able to classify more than 85% of the infants. About 64% had a prototypic syndrome at onset, such as West syndrome, which accounted for 33% of all SEI, or Dravet syndrome, which was diagnosed in 3%.
The prevalence of the prototypic neonatal and early infantile epileptic syndromes was notably higher than previously reported by others: EIMFS accounted for 9% of total SEI, early infantile epileptic encephalopathy (EIEE) for 7%, and early myoclonic encephalopathy (EME) for 2%. This translated to an incidence of 1 in 28,000 live births for EIEE, 1 in 111,000 for EME, and 1 in 22,500 for EIMFS.
“While neither EIEE nor EIMFS are common, these incidences are actually not that much lower than the reported incidence of Dravet syndrome,” the neurologist pointed out.
About 36% of SEI didn’t fit into any of the prototypic syndromes. However, more than half of this subgroup, or 19% of total SEI, were prototypic syndrome like, a designation Dr. Howell and her coworkers used for cases that possessed most but not all of the well-recognized features of a particular prototypic syndrome; for example, West syndrome–like seizures but without hypsarrhythmia. Whether these prototypic syndrome-like SEI have etiologies and outcomes similar to or distinct from the prototypic syndromes remains a topic for further study.
SEI etiologies
A total of 14 patients had SEI because of an acquired syndrome attributed to brain injury, 31 were because of brain malformation, 21 involved single gene disorders, 9 were of chromosomal etiology, and 7 had a metabolic cause.
The key finding with regard to etiology was the glaring difference between children with West syndrome, its variants, or unifocal epilepsies as compared with the rest of the SEI patients. Those with West syndrome, a West syndrome–like designation, or unifocal epilepsies most commonly had a structural etiology for their SEI. Indeed, of the 52 children with West syndrome or a variant, 10 had an acquired brain injury as their etiology and 17 had a brain malformation. And of the 12 patients with unifocal SEI, 1 had a brain injury and 9 had brain malformations.
In contrast, children with neonatal or early infantile epileptic syndromes had predominantly genetic rather than structural etiologies. Of the 20 children with EIEE, EIMFS, or EME, none had brain injury as the etiology, only 1 had a brain malformation, but 9 had a single gene or chromosomal etiology.
Outcomes
“The outcome data highlight the extreme severity of SEI and the imperative for novel treatments: 16% mortality overall, so one in six was deceased by age 2 years. The infants who died after the neonatal period all had profound delays, and almost all had ongoing seizures until their death. Most survivors also had developmental delay, with severity ranging from mild to moderate in 49% to severe/profound in 41%. Just 10 of 114 children had normal development,” Dr. Howell reported.
However, there was a notable difference in outcomes between the various syndromes, and this information is highly relevant prognostically. Of the 20 children with neonatal and early infantile epileptic syndromes, 11 died and the other 9 had profound developmental delay. In contrast, the outlook was far better for children with West syndrome, West syndrome–like variants, or focal epilepsies: Among 64 affected patients, there were just 2 deaths, normal development in 9 patients, mild to moderate developmental delay in 34, and severe/profound delay in 19.
Dr. Howell reported having no financial conflicts regarding this study, which was supported by governmental research grants.
SOURCE: Howell KB et al. IEC 2019, Abstract P053.
BANGKOK – Katherine B. Howell, MD, reported at the International Epilepsy Congress.
“This is an important finding. It’s a considerably larger number than might have been expected and likely has two contributing factors. Neonatal seizures were previously not considered epilepsy, so many previous studies excluded neonates and the conditions were underrecognized. And our large number of ictal EEGs allowed identification of ictal activation, which is a feature of EIMFS [epilepsy of infancy with migrating focal seizures]. Without those ictal recordings, the diagnosis of EIMFS may not have been made,” according to Dr. Howell, a neurologist at the Royal Children’s Hospital and University of Melbourne.
She presented a population-based study of all infants born with severe epilepsies of infancy (SEI) during a 2-year period in the Australian state of Victoria, which is considered an ideal environment for epidemiologic studies because government-funded health care is available to all. SEI was defined as seizures beginning before age 18 months, occurring at a rate of at least one per day for 1 week or weekly for 1 month, refractory to adequate trials of at least two antiepileptic drugs, and accompanied by an epileptiform EEG abnormality. Her focus was on the electroclinical phenotypes of the affected children because of the high clinical utility of this information.
“Assigning an epileptic syndrome is highly useful for clinician-to-clinician communication of an infant’s phenotype. It guides investigation of etiology and possibly selection of optimal therapy, such as steroids in West syndrome. And it can inform prognosis,” Dr. Howell said at the congress sponsored by the International League Against Epilepsy.
She and her coinvestigators analyzed the detailed records of all 114 infants with SEI born during the study period. The incidence was 1 in 2,000 live births.
“Among infants with epilepsy, this patient group with SEI is most critical to better understand. Effective treatment is often not available, the seizure and developmental outcomes are frequently devastating, and the health burden massive,” the neurologist observed.
The full spectrum of SEI
With the help of ictal EEGs, home seizure recordings, MRI scans, and genomic testing, the investigators were able to classify more than 85% of the infants. About 64% had a prototypic syndrome at onset, such as West syndrome, which accounted for 33% of all SEI, or Dravet syndrome, which was diagnosed in 3%.
The prevalence of the prototypic neonatal and early infantile epileptic syndromes was notably higher than previously reported by others: EIMFS accounted for 9% of total SEI, early infantile epileptic encephalopathy (EIEE) for 7%, and early myoclonic encephalopathy (EME) for 2%. This translated to an incidence of 1 in 28,000 live births for EIEE, 1 in 111,000 for EME, and 1 in 22,500 for EIMFS.
“While neither EIEE nor EIMFS are common, these incidences are actually not that much lower than the reported incidence of Dravet syndrome,” the neurologist pointed out.
About 36% of SEI didn’t fit into any of the prototypic syndromes. However, more than half of this subgroup, or 19% of total SEI, were prototypic syndrome like, a designation Dr. Howell and her coworkers used for cases that possessed most but not all of the well-recognized features of a particular prototypic syndrome; for example, West syndrome–like seizures but without hypsarrhythmia. Whether these prototypic syndrome-like SEI have etiologies and outcomes similar to or distinct from the prototypic syndromes remains a topic for further study.
SEI etiologies
A total of 14 patients had SEI because of an acquired syndrome attributed to brain injury, 31 were because of brain malformation, 21 involved single gene disorders, 9 were of chromosomal etiology, and 7 had a metabolic cause.
The key finding with regard to etiology was the glaring difference between children with West syndrome, its variants, or unifocal epilepsies as compared with the rest of the SEI patients. Those with West syndrome, a West syndrome–like designation, or unifocal epilepsies most commonly had a structural etiology for their SEI. Indeed, of the 52 children with West syndrome or a variant, 10 had an acquired brain injury as their etiology and 17 had a brain malformation. And of the 12 patients with unifocal SEI, 1 had a brain injury and 9 had brain malformations.
In contrast, children with neonatal or early infantile epileptic syndromes had predominantly genetic rather than structural etiologies. Of the 20 children with EIEE, EIMFS, or EME, none had brain injury as the etiology, only 1 had a brain malformation, but 9 had a single gene or chromosomal etiology.
Outcomes
“The outcome data highlight the extreme severity of SEI and the imperative for novel treatments: 16% mortality overall, so one in six was deceased by age 2 years. The infants who died after the neonatal period all had profound delays, and almost all had ongoing seizures until their death. Most survivors also had developmental delay, with severity ranging from mild to moderate in 49% to severe/profound in 41%. Just 10 of 114 children had normal development,” Dr. Howell reported.
However, there was a notable difference in outcomes between the various syndromes, and this information is highly relevant prognostically. Of the 20 children with neonatal and early infantile epileptic syndromes, 11 died and the other 9 had profound developmental delay. In contrast, the outlook was far better for children with West syndrome, West syndrome–like variants, or focal epilepsies: Among 64 affected patients, there were just 2 deaths, normal development in 9 patients, mild to moderate developmental delay in 34, and severe/profound delay in 19.
Dr. Howell reported having no financial conflicts regarding this study, which was supported by governmental research grants.
SOURCE: Howell KB et al. IEC 2019, Abstract P053.
BANGKOK – Katherine B. Howell, MD, reported at the International Epilepsy Congress.
“This is an important finding. It’s a considerably larger number than might have been expected and likely has two contributing factors. Neonatal seizures were previously not considered epilepsy, so many previous studies excluded neonates and the conditions were underrecognized. And our large number of ictal EEGs allowed identification of ictal activation, which is a feature of EIMFS [epilepsy of infancy with migrating focal seizures]. Without those ictal recordings, the diagnosis of EIMFS may not have been made,” according to Dr. Howell, a neurologist at the Royal Children’s Hospital and University of Melbourne.
She presented a population-based study of all infants born with severe epilepsies of infancy (SEI) during a 2-year period in the Australian state of Victoria, which is considered an ideal environment for epidemiologic studies because government-funded health care is available to all. SEI was defined as seizures beginning before age 18 months, occurring at a rate of at least one per day for 1 week or weekly for 1 month, refractory to adequate trials of at least two antiepileptic drugs, and accompanied by an epileptiform EEG abnormality. Her focus was on the electroclinical phenotypes of the affected children because of the high clinical utility of this information.
“Assigning an epileptic syndrome is highly useful for clinician-to-clinician communication of an infant’s phenotype. It guides investigation of etiology and possibly selection of optimal therapy, such as steroids in West syndrome. And it can inform prognosis,” Dr. Howell said at the congress sponsored by the International League Against Epilepsy.
She and her coinvestigators analyzed the detailed records of all 114 infants with SEI born during the study period. The incidence was 1 in 2,000 live births.
“Among infants with epilepsy, this patient group with SEI is most critical to better understand. Effective treatment is often not available, the seizure and developmental outcomes are frequently devastating, and the health burden massive,” the neurologist observed.
The full spectrum of SEI
With the help of ictal EEGs, home seizure recordings, MRI scans, and genomic testing, the investigators were able to classify more than 85% of the infants. About 64% had a prototypic syndrome at onset, such as West syndrome, which accounted for 33% of all SEI, or Dravet syndrome, which was diagnosed in 3%.
The prevalence of the prototypic neonatal and early infantile epileptic syndromes was notably higher than previously reported by others: EIMFS accounted for 9% of total SEI, early infantile epileptic encephalopathy (EIEE) for 7%, and early myoclonic encephalopathy (EME) for 2%. This translated to an incidence of 1 in 28,000 live births for EIEE, 1 in 111,000 for EME, and 1 in 22,500 for EIMFS.
“While neither EIEE nor EIMFS are common, these incidences are actually not that much lower than the reported incidence of Dravet syndrome,” the neurologist pointed out.
About 36% of SEI didn’t fit into any of the prototypic syndromes. However, more than half of this subgroup, or 19% of total SEI, were prototypic syndrome like, a designation Dr. Howell and her coworkers used for cases that possessed most but not all of the well-recognized features of a particular prototypic syndrome; for example, West syndrome–like seizures but without hypsarrhythmia. Whether these prototypic syndrome-like SEI have etiologies and outcomes similar to or distinct from the prototypic syndromes remains a topic for further study.
SEI etiologies
A total of 14 patients had SEI because of an acquired syndrome attributed to brain injury, 31 were because of brain malformation, 21 involved single gene disorders, 9 were of chromosomal etiology, and 7 had a metabolic cause.
The key finding with regard to etiology was the glaring difference between children with West syndrome, its variants, or unifocal epilepsies as compared with the rest of the SEI patients. Those with West syndrome, a West syndrome–like designation, or unifocal epilepsies most commonly had a structural etiology for their SEI. Indeed, of the 52 children with West syndrome or a variant, 10 had an acquired brain injury as their etiology and 17 had a brain malformation. And of the 12 patients with unifocal SEI, 1 had a brain injury and 9 had brain malformations.
In contrast, children with neonatal or early infantile epileptic syndromes had predominantly genetic rather than structural etiologies. Of the 20 children with EIEE, EIMFS, or EME, none had brain injury as the etiology, only 1 had a brain malformation, but 9 had a single gene or chromosomal etiology.
Outcomes
“The outcome data highlight the extreme severity of SEI and the imperative for novel treatments: 16% mortality overall, so one in six was deceased by age 2 years. The infants who died after the neonatal period all had profound delays, and almost all had ongoing seizures until their death. Most survivors also had developmental delay, with severity ranging from mild to moderate in 49% to severe/profound in 41%. Just 10 of 114 children had normal development,” Dr. Howell reported.
However, there was a notable difference in outcomes between the various syndromes, and this information is highly relevant prognostically. Of the 20 children with neonatal and early infantile epileptic syndromes, 11 died and the other 9 had profound developmental delay. In contrast, the outlook was far better for children with West syndrome, West syndrome–like variants, or focal epilepsies: Among 64 affected patients, there were just 2 deaths, normal development in 9 patients, mild to moderate developmental delay in 34, and severe/profound delay in 19.
Dr. Howell reported having no financial conflicts regarding this study, which was supported by governmental research grants.
SOURCE: Howell KB et al. IEC 2019, Abstract P053.
REPORTING FROM IEC 2019
Ibrutinib/rituximab effective, safe as frontline treatment for older patients with MCL
LUGANO, SWITZERLAND – The chemotherapy-free combination of ibrutinib (Imbruvica) and rituximab is highly effective as frontline therapy for older, transplant-ineligible patients with nonblastoid mantle cell lymphoma, according to investigators.
In a phase 2 study of patients with a median age of 71 years, 38 of 41 patients (93%) had an objective response, and the regimen was both safe and easy to administer, reported Preetesh Jain, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.
“The adverse event profile was generally favorable, with specific monitoring recommended for patients with cardiovascular comorbidities and a history of atrial fibrillation,” he said at the International Conference on Malignant Lymphoma.
The investigators enrolled 48 patients aged 65 years and older with previously untreated mantle cell lymphoma (MCL), of whom 41 were evaluable for the primary endpoints of overall response rate (ORR) and safety. The patients had good performance status and normal organ function, with the largest tumor size less than 10 cm. Patients with atrial fibrillation could participate, if the fibrillation was controlled. Patients with Ki-67 protein levels of 50% or greater and blastoid/pleomorphic histology were excluded.
Patients were treated with ibrutinib 560 mg orally daily for each 28-day cycle, with therapy continued until disease progression, or until therapy was stopped for any other reason. Patients also received intravenous rituximab 375 mg/m2 on days 1, 8, 15 and 22, plus or minus one day for cycle 1, on day 1 of cycles 3-8, and on day 1 of every other cycle for up to 2 years.
Of the 41 patients evaluable for response, 26 (64%) had a complete response (CR) and 12 (29%) had a partial response. Three additional patients had stable disease, for an objective response rate of 93%.
Of 34 patients with PET scans, all had negative scans. Of 37 patients evaluable for minimal residual disease (MRD) by flow cytometry, 21 (58%) were MRD negative.
Patients with low or intermediate Mantle Cell Lymphoma International Prognostic Index (MIPI) scores had a higher ORR (100% vs. 89% for patients with high MIPI scores), and patients with low Ki-67 levels had a higher response rate than that of patients with KI-67 of 30% or greater (80% vs. 87%).
Neither median 3-year progression-free survival nor median 3-year overall survival have been reached, with respective 3-year rates of 87% and 95%.
Four patients experienced disease progression at 4, 10, 13 and 33 months of treatment. Three of these patients had disease that had transformed to blastoid/pleomorphic variant, two had Ki-67 of 30% or greater, one had mutations in TP53, and one had FAT1 and SF3B1 mutations.
Two patients died after ibrutinib therapy, one who had discontinued therapy because of bleeding, and the other who died on treatment at 13 months from transformed disease. Both of these patients had high Ki-67 levels.
Grade 3 or 4 hematological adverse events were neutropenia in four patients, and thrombocytopenia in two patients. There were no cases of grade 3 or 4 anemia.
Grade 3 or 4 nonhematological adverse events were fatigue, myalgia, and atrial fibrillation in seven patients each, diarrhea in six patients, and petechiae/bleeding in three patients.
Patients will continue to be followed for late adverse events, secondary cancers, and relapses, and further studies on clonal evolution, mutation profiling, and MRD are ongoing and will be reported at a later date, Dr. Jain said.
The National Cancer Institute supported the study. Dr. Jain reported having no financial disclosures.
SOURCE: Jain P et al. 15-ICML. Abstract 011.
LUGANO, SWITZERLAND – The chemotherapy-free combination of ibrutinib (Imbruvica) and rituximab is highly effective as frontline therapy for older, transplant-ineligible patients with nonblastoid mantle cell lymphoma, according to investigators.
In a phase 2 study of patients with a median age of 71 years, 38 of 41 patients (93%) had an objective response, and the regimen was both safe and easy to administer, reported Preetesh Jain, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.
“The adverse event profile was generally favorable, with specific monitoring recommended for patients with cardiovascular comorbidities and a history of atrial fibrillation,” he said at the International Conference on Malignant Lymphoma.
The investigators enrolled 48 patients aged 65 years and older with previously untreated mantle cell lymphoma (MCL), of whom 41 were evaluable for the primary endpoints of overall response rate (ORR) and safety. The patients had good performance status and normal organ function, with the largest tumor size less than 10 cm. Patients with atrial fibrillation could participate, if the fibrillation was controlled. Patients with Ki-67 protein levels of 50% or greater and blastoid/pleomorphic histology were excluded.
Patients were treated with ibrutinib 560 mg orally daily for each 28-day cycle, with therapy continued until disease progression, or until therapy was stopped for any other reason. Patients also received intravenous rituximab 375 mg/m2 on days 1, 8, 15 and 22, plus or minus one day for cycle 1, on day 1 of cycles 3-8, and on day 1 of every other cycle for up to 2 years.
Of the 41 patients evaluable for response, 26 (64%) had a complete response (CR) and 12 (29%) had a partial response. Three additional patients had stable disease, for an objective response rate of 93%.
Of 34 patients with PET scans, all had negative scans. Of 37 patients evaluable for minimal residual disease (MRD) by flow cytometry, 21 (58%) were MRD negative.
Patients with low or intermediate Mantle Cell Lymphoma International Prognostic Index (MIPI) scores had a higher ORR (100% vs. 89% for patients with high MIPI scores), and patients with low Ki-67 levels had a higher response rate than that of patients with KI-67 of 30% or greater (80% vs. 87%).
Neither median 3-year progression-free survival nor median 3-year overall survival have been reached, with respective 3-year rates of 87% and 95%.
Four patients experienced disease progression at 4, 10, 13 and 33 months of treatment. Three of these patients had disease that had transformed to blastoid/pleomorphic variant, two had Ki-67 of 30% or greater, one had mutations in TP53, and one had FAT1 and SF3B1 mutations.
Two patients died after ibrutinib therapy, one who had discontinued therapy because of bleeding, and the other who died on treatment at 13 months from transformed disease. Both of these patients had high Ki-67 levels.
Grade 3 or 4 hematological adverse events were neutropenia in four patients, and thrombocytopenia in two patients. There were no cases of grade 3 or 4 anemia.
Grade 3 or 4 nonhematological adverse events were fatigue, myalgia, and atrial fibrillation in seven patients each, diarrhea in six patients, and petechiae/bleeding in three patients.
Patients will continue to be followed for late adverse events, secondary cancers, and relapses, and further studies on clonal evolution, mutation profiling, and MRD are ongoing and will be reported at a later date, Dr. Jain said.
The National Cancer Institute supported the study. Dr. Jain reported having no financial disclosures.
SOURCE: Jain P et al. 15-ICML. Abstract 011.
LUGANO, SWITZERLAND – The chemotherapy-free combination of ibrutinib (Imbruvica) and rituximab is highly effective as frontline therapy for older, transplant-ineligible patients with nonblastoid mantle cell lymphoma, according to investigators.
In a phase 2 study of patients with a median age of 71 years, 38 of 41 patients (93%) had an objective response, and the regimen was both safe and easy to administer, reported Preetesh Jain, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.
“The adverse event profile was generally favorable, with specific monitoring recommended for patients with cardiovascular comorbidities and a history of atrial fibrillation,” he said at the International Conference on Malignant Lymphoma.
The investigators enrolled 48 patients aged 65 years and older with previously untreated mantle cell lymphoma (MCL), of whom 41 were evaluable for the primary endpoints of overall response rate (ORR) and safety. The patients had good performance status and normal organ function, with the largest tumor size less than 10 cm. Patients with atrial fibrillation could participate, if the fibrillation was controlled. Patients with Ki-67 protein levels of 50% or greater and blastoid/pleomorphic histology were excluded.
Patients were treated with ibrutinib 560 mg orally daily for each 28-day cycle, with therapy continued until disease progression, or until therapy was stopped for any other reason. Patients also received intravenous rituximab 375 mg/m2 on days 1, 8, 15 and 22, plus or minus one day for cycle 1, on day 1 of cycles 3-8, and on day 1 of every other cycle for up to 2 years.
Of the 41 patients evaluable for response, 26 (64%) had a complete response (CR) and 12 (29%) had a partial response. Three additional patients had stable disease, for an objective response rate of 93%.
Of 34 patients with PET scans, all had negative scans. Of 37 patients evaluable for minimal residual disease (MRD) by flow cytometry, 21 (58%) were MRD negative.
Patients with low or intermediate Mantle Cell Lymphoma International Prognostic Index (MIPI) scores had a higher ORR (100% vs. 89% for patients with high MIPI scores), and patients with low Ki-67 levels had a higher response rate than that of patients with KI-67 of 30% or greater (80% vs. 87%).
Neither median 3-year progression-free survival nor median 3-year overall survival have been reached, with respective 3-year rates of 87% and 95%.
Four patients experienced disease progression at 4, 10, 13 and 33 months of treatment. Three of these patients had disease that had transformed to blastoid/pleomorphic variant, two had Ki-67 of 30% or greater, one had mutations in TP53, and one had FAT1 and SF3B1 mutations.
Two patients died after ibrutinib therapy, one who had discontinued therapy because of bleeding, and the other who died on treatment at 13 months from transformed disease. Both of these patients had high Ki-67 levels.
Grade 3 or 4 hematological adverse events were neutropenia in four patients, and thrombocytopenia in two patients. There were no cases of grade 3 or 4 anemia.
Grade 3 or 4 nonhematological adverse events were fatigue, myalgia, and atrial fibrillation in seven patients each, diarrhea in six patients, and petechiae/bleeding in three patients.
Patients will continue to be followed for late adverse events, secondary cancers, and relapses, and further studies on clonal evolution, mutation profiling, and MRD are ongoing and will be reported at a later date, Dr. Jain said.
The National Cancer Institute supported the study. Dr. Jain reported having no financial disclosures.
SOURCE: Jain P et al. 15-ICML. Abstract 011.
REPORTING FROM 15-ICML
Bevacizumab-erlotinib combo falls short in EGFR-mutant advanced NSCLC
according to a multicenter, phase 2, randomized, controlled trial.
“The development of erlotinib as a first-line therapy was an important advance, but there was interest in improving the efficacy of erlotinib,” noted the investigators, led by Thomas E. Stinchcombe, MD, of the Duke Cancer Institute in Durham, N.C. Preclinical data suggested that adding an antiangiogenic agent could overcome resistance, and subgroup analyses of a phase 3 trial hinted at greater efficacy of this combination in patients with EGFR-mutant disease (Lancet. 2011;377:1846-54).
The new trial was conducted among 88 patients with previously untreated stage 4 EGFR-mutant NSCLC eligible to receive bevacizumab. Two-thirds had an EGFR exon 19 deletion.
The patients were assigned evenly to receive erlotinib (Tarceva), an EGFR tyrosine kinase inhibitor, either alone or in combination with bevacizumab (Avastin), an antibody directed against vascular endothelial growth factor.
Results reported in JAMA Oncology showed that, during a median follow-up of 33 months, median progression-free survival (PFS) – the trial’s primary endpoint – was 17.9 months with the combination and 13.5 months with erlotinib alone, a nonsignificant difference (hazard ratio, 0.81; P = .39).
There was also no significant difference between groups in objective response rate (81% vs. 83%; P = .81) and overall survival (median, 32.4 vs. 50.6 months; HR, 1.41; P = .33).
Relative to the erlotinib monotherapy group, the combination therapy group had higher rates of grade 3 or worse acneiform rash (26% vs. 16%), hypertension (40% vs. 20%), and proteinuria (12% vs. 0%), but a lower rate of grade 3 or worse diarrhea (9% vs. 13%).
“Our study, unlike previous randomized clinical trials, did not reveal a significant improvement in PFS with the combination of erlotinib and bevacizumab. ... One consideration is that our trial used investigator assessment of response and disease progression, whereas previous randomized trials used blinded independent radiologic review,” Dr. Stinchcombe and coinvestigators summarized.
“Future studies will investigate novel osimertinib [Tagrisso] combinations and molecular markers to identify patients most likely to experience disease progression with single-agent EGFR TKIs,” they concluded.
Dr. Stinchcombe reported no relevant conflicts of interest. The trial was supported by Genentech/Roche.
SOURCE: Stinchcombe TE et al. JAMA Oncol. 2019 Aug 8. doi: 10.1001/jamaoncol.2019.1847.
according to a multicenter, phase 2, randomized, controlled trial.
“The development of erlotinib as a first-line therapy was an important advance, but there was interest in improving the efficacy of erlotinib,” noted the investigators, led by Thomas E. Stinchcombe, MD, of the Duke Cancer Institute in Durham, N.C. Preclinical data suggested that adding an antiangiogenic agent could overcome resistance, and subgroup analyses of a phase 3 trial hinted at greater efficacy of this combination in patients with EGFR-mutant disease (Lancet. 2011;377:1846-54).
The new trial was conducted among 88 patients with previously untreated stage 4 EGFR-mutant NSCLC eligible to receive bevacizumab. Two-thirds had an EGFR exon 19 deletion.
The patients were assigned evenly to receive erlotinib (Tarceva), an EGFR tyrosine kinase inhibitor, either alone or in combination with bevacizumab (Avastin), an antibody directed against vascular endothelial growth factor.
Results reported in JAMA Oncology showed that, during a median follow-up of 33 months, median progression-free survival (PFS) – the trial’s primary endpoint – was 17.9 months with the combination and 13.5 months with erlotinib alone, a nonsignificant difference (hazard ratio, 0.81; P = .39).
There was also no significant difference between groups in objective response rate (81% vs. 83%; P = .81) and overall survival (median, 32.4 vs. 50.6 months; HR, 1.41; P = .33).
Relative to the erlotinib monotherapy group, the combination therapy group had higher rates of grade 3 or worse acneiform rash (26% vs. 16%), hypertension (40% vs. 20%), and proteinuria (12% vs. 0%), but a lower rate of grade 3 or worse diarrhea (9% vs. 13%).
“Our study, unlike previous randomized clinical trials, did not reveal a significant improvement in PFS with the combination of erlotinib and bevacizumab. ... One consideration is that our trial used investigator assessment of response and disease progression, whereas previous randomized trials used blinded independent radiologic review,” Dr. Stinchcombe and coinvestigators summarized.
“Future studies will investigate novel osimertinib [Tagrisso] combinations and molecular markers to identify patients most likely to experience disease progression with single-agent EGFR TKIs,” they concluded.
Dr. Stinchcombe reported no relevant conflicts of interest. The trial was supported by Genentech/Roche.
SOURCE: Stinchcombe TE et al. JAMA Oncol. 2019 Aug 8. doi: 10.1001/jamaoncol.2019.1847.
according to a multicenter, phase 2, randomized, controlled trial.
“The development of erlotinib as a first-line therapy was an important advance, but there was interest in improving the efficacy of erlotinib,” noted the investigators, led by Thomas E. Stinchcombe, MD, of the Duke Cancer Institute in Durham, N.C. Preclinical data suggested that adding an antiangiogenic agent could overcome resistance, and subgroup analyses of a phase 3 trial hinted at greater efficacy of this combination in patients with EGFR-mutant disease (Lancet. 2011;377:1846-54).
The new trial was conducted among 88 patients with previously untreated stage 4 EGFR-mutant NSCLC eligible to receive bevacizumab. Two-thirds had an EGFR exon 19 deletion.
The patients were assigned evenly to receive erlotinib (Tarceva), an EGFR tyrosine kinase inhibitor, either alone or in combination with bevacizumab (Avastin), an antibody directed against vascular endothelial growth factor.
Results reported in JAMA Oncology showed that, during a median follow-up of 33 months, median progression-free survival (PFS) – the trial’s primary endpoint – was 17.9 months with the combination and 13.5 months with erlotinib alone, a nonsignificant difference (hazard ratio, 0.81; P = .39).
There was also no significant difference between groups in objective response rate (81% vs. 83%; P = .81) and overall survival (median, 32.4 vs. 50.6 months; HR, 1.41; P = .33).
Relative to the erlotinib monotherapy group, the combination therapy group had higher rates of grade 3 or worse acneiform rash (26% vs. 16%), hypertension (40% vs. 20%), and proteinuria (12% vs. 0%), but a lower rate of grade 3 or worse diarrhea (9% vs. 13%).
“Our study, unlike previous randomized clinical trials, did not reveal a significant improvement in PFS with the combination of erlotinib and bevacizumab. ... One consideration is that our trial used investigator assessment of response and disease progression, whereas previous randomized trials used blinded independent radiologic review,” Dr. Stinchcombe and coinvestigators summarized.
“Future studies will investigate novel osimertinib [Tagrisso] combinations and molecular markers to identify patients most likely to experience disease progression with single-agent EGFR TKIs,” they concluded.
Dr. Stinchcombe reported no relevant conflicts of interest. The trial was supported by Genentech/Roche.
SOURCE: Stinchcombe TE et al. JAMA Oncol. 2019 Aug 8. doi: 10.1001/jamaoncol.2019.1847.
FROM JAMA ONCOLOGY
PROMIS tools provide useful data for managing rheumatology patients
LAKE BUENA VISTA, FLA. –
The PROMIS tools – which like most patient-reported outcome (PRO) measurement tools are designed to evaluate and monitor physical, mental, and social health – can be used both for the general population and for individuals living with chronic conditions, Dr. Curtis, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham (UAB), said at the annual meeting of the Florida Society of Rheumatology.
The tools take a deeper dive into various symptoms and their effects; for instance, with respect to physical health, they measure fatigue, physical function, sleep disturbance, pain intensity, and pain interference – the extent to which pain “messes your patient’s life up,” explained Dr. Curtis, who also is codirector of the UAB Pharmacoepidemiology and Pharmacoeconomics Unit.
Additional physical health domains that PROs measure include dyspnea, gastrointestinal symptoms, pain behavior, pain quality, sexual function, and sleep-related impairment.
These are “things that, honestly, we don’t talk about much as a field, but absolutely affect patients with autoimmune diseases,” he said. “You know, sexual function – that doesn’t come up in my practice spontaneously very often, but there are ways you can quantify that, and for many patients that’s actually a big deal.”
The domains measured by PROMIS tools for mental health look at anxiety and depression, but also delve into alcohol use, anger, cognitive function, life satisfaction, self-efficacy for managing chronic conditions, substance use, and more. The domains for social health address ability to participate in social roles and activities, as well as companionship, satisfaction with social roles and activity, social isolation, and social support.
“You can’t go on a hike with friends [and] be far from a bathroom, because you have bad arthritis and you have Crohn’s disease. Well, that’s kind of an important thing that may or may not come up in your discussions about inflammatory arthritis associated with [inflammatory bowel disease],” he said.
Another example is a patient who is embarrassed attending social functions or wearing a swimsuit because of really bad psoriasis.
“These are the kinds of things that I’m suggesting you and I probably want to measure if we’re providing holistic care to rheumatology patients,” Dr. Curtis said.
The PROMIS tools provide a simple, user-friendly means for doing so in English, Spanish, and many other languages, he noted.
All the scales use the same 1-100 scoring range, which simplifies measurements. They are available for free by download and can be printed or used electronically for use in the office, at home, on the web, and via smartphone.
The NIH developed the PROMIS tools several years ago and validated them for multiple chronic disease populations, Dr. Curtis said, adding that the tools include multiple individual domains and overall “profiles” of varying lengths.
Most are fixed-length scales that are between 4 and 10 questions and can be completed within 30-60 seconds per scale, so several scales can be completed within 5-10 minutes.
However, some scales are longer and provide greater detail.
“The nice thing is that if you ask a few more questions you can get more precise information – there’s more of a floor and ceiling. You can detect people who do really well. You can distinguish between the marathon runners and the 5K-ers and the people who can walk 2 miles but aren’t going to run a race,” he explained.
Further, the PROMIS tools, like the 36-item Short Form Health Survey (SF-36), are benchmarked against the U.S. adult population, allowing for assessment of how a specific drug or treatment “impacts your arthritis patient on a scale that would also be relevant for somebody who doesn’t have arthritis, they have diabetes.”
The metrics and scales are the same, and that can be helpful when trying to get a payer to pay for a particular drug, he said.
“None of these are rheumatology specific; this puts PROs into a language that can help rheumatology contend for the value of the care that we provide on a scale that would be relevant for any other chronic illness, even for nonrheumatology patients,” he explained.
In addition, minimally important differences (group mean change of about 2-3 units) and minimally clinical important differences for individuals (5 units) have been established.
“So we know what the numbers mean, and this is true for all of the scales,” he said.
PROMIS tools also include computer-adaptive testing (CAT) versions, which helps to personalize the scales to provide more precise information for a given patient and eliminate irrelevant information.
Of note, PROMIS health measures are among the data that can be tracked on a smartphone using Arthritis Power, an arthritis research registry developed with the help of a recent infrastructure grant awarded to the Center for Education and Research and Therapeutics of Musculoskeletal Disorders at UAB, Dr. Curtis said.
The measures were also shown in the AWARE study to track closely with other measures, including the Clinical Disease Activity Index (CDAI), and with patient improvement on therapy.
“So these PROMIS scores are tracking with things that you and I are familiar with ... and it looks like these scores are faithfully tracking, over time, patients getting better on therapies that we would expect them to,” he said. “I think this is additional validation – not just from the National Institutes of Health and a decade of research by lots of different groups, but in our own field – that these actually correlate with disease activity ... and that when you start an effective therapy like a [tumor necrosis factor inhibitor] they’re going to improve as you would anticipate.”
Dr. Curtis reported funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Patient-Centered Outcomes Research Institute. He has also consulted for or received research grants from Amgen, AbbVie, Bristol-Myers Squibb, CORRONA, Lilly, Janssen, Myriad, Novartis, Roche, Pfizer, and Sanofi/Regeneron.
LAKE BUENA VISTA, FLA. –
The PROMIS tools – which like most patient-reported outcome (PRO) measurement tools are designed to evaluate and monitor physical, mental, and social health – can be used both for the general population and for individuals living with chronic conditions, Dr. Curtis, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham (UAB), said at the annual meeting of the Florida Society of Rheumatology.
The tools take a deeper dive into various symptoms and their effects; for instance, with respect to physical health, they measure fatigue, physical function, sleep disturbance, pain intensity, and pain interference – the extent to which pain “messes your patient’s life up,” explained Dr. Curtis, who also is codirector of the UAB Pharmacoepidemiology and Pharmacoeconomics Unit.
Additional physical health domains that PROs measure include dyspnea, gastrointestinal symptoms, pain behavior, pain quality, sexual function, and sleep-related impairment.
These are “things that, honestly, we don’t talk about much as a field, but absolutely affect patients with autoimmune diseases,” he said. “You know, sexual function – that doesn’t come up in my practice spontaneously very often, but there are ways you can quantify that, and for many patients that’s actually a big deal.”
The domains measured by PROMIS tools for mental health look at anxiety and depression, but also delve into alcohol use, anger, cognitive function, life satisfaction, self-efficacy for managing chronic conditions, substance use, and more. The domains for social health address ability to participate in social roles and activities, as well as companionship, satisfaction with social roles and activity, social isolation, and social support.
“You can’t go on a hike with friends [and] be far from a bathroom, because you have bad arthritis and you have Crohn’s disease. Well, that’s kind of an important thing that may or may not come up in your discussions about inflammatory arthritis associated with [inflammatory bowel disease],” he said.
Another example is a patient who is embarrassed attending social functions or wearing a swimsuit because of really bad psoriasis.
“These are the kinds of things that I’m suggesting you and I probably want to measure if we’re providing holistic care to rheumatology patients,” Dr. Curtis said.
The PROMIS tools provide a simple, user-friendly means for doing so in English, Spanish, and many other languages, he noted.
All the scales use the same 1-100 scoring range, which simplifies measurements. They are available for free by download and can be printed or used electronically for use in the office, at home, on the web, and via smartphone.
The NIH developed the PROMIS tools several years ago and validated them for multiple chronic disease populations, Dr. Curtis said, adding that the tools include multiple individual domains and overall “profiles” of varying lengths.
Most are fixed-length scales that are between 4 and 10 questions and can be completed within 30-60 seconds per scale, so several scales can be completed within 5-10 minutes.
However, some scales are longer and provide greater detail.
“The nice thing is that if you ask a few more questions you can get more precise information – there’s more of a floor and ceiling. You can detect people who do really well. You can distinguish between the marathon runners and the 5K-ers and the people who can walk 2 miles but aren’t going to run a race,” he explained.
Further, the PROMIS tools, like the 36-item Short Form Health Survey (SF-36), are benchmarked against the U.S. adult population, allowing for assessment of how a specific drug or treatment “impacts your arthritis patient on a scale that would also be relevant for somebody who doesn’t have arthritis, they have diabetes.”
The metrics and scales are the same, and that can be helpful when trying to get a payer to pay for a particular drug, he said.
“None of these are rheumatology specific; this puts PROs into a language that can help rheumatology contend for the value of the care that we provide on a scale that would be relevant for any other chronic illness, even for nonrheumatology patients,” he explained.
In addition, minimally important differences (group mean change of about 2-3 units) and minimally clinical important differences for individuals (5 units) have been established.
“So we know what the numbers mean, and this is true for all of the scales,” he said.
PROMIS tools also include computer-adaptive testing (CAT) versions, which helps to personalize the scales to provide more precise information for a given patient and eliminate irrelevant information.
Of note, PROMIS health measures are among the data that can be tracked on a smartphone using Arthritis Power, an arthritis research registry developed with the help of a recent infrastructure grant awarded to the Center for Education and Research and Therapeutics of Musculoskeletal Disorders at UAB, Dr. Curtis said.
The measures were also shown in the AWARE study to track closely with other measures, including the Clinical Disease Activity Index (CDAI), and with patient improvement on therapy.
“So these PROMIS scores are tracking with things that you and I are familiar with ... and it looks like these scores are faithfully tracking, over time, patients getting better on therapies that we would expect them to,” he said. “I think this is additional validation – not just from the National Institutes of Health and a decade of research by lots of different groups, but in our own field – that these actually correlate with disease activity ... and that when you start an effective therapy like a [tumor necrosis factor inhibitor] they’re going to improve as you would anticipate.”
Dr. Curtis reported funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Patient-Centered Outcomes Research Institute. He has also consulted for or received research grants from Amgen, AbbVie, Bristol-Myers Squibb, CORRONA, Lilly, Janssen, Myriad, Novartis, Roche, Pfizer, and Sanofi/Regeneron.
LAKE BUENA VISTA, FLA. –
The PROMIS tools – which like most patient-reported outcome (PRO) measurement tools are designed to evaluate and monitor physical, mental, and social health – can be used both for the general population and for individuals living with chronic conditions, Dr. Curtis, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham (UAB), said at the annual meeting of the Florida Society of Rheumatology.
The tools take a deeper dive into various symptoms and their effects; for instance, with respect to physical health, they measure fatigue, physical function, sleep disturbance, pain intensity, and pain interference – the extent to which pain “messes your patient’s life up,” explained Dr. Curtis, who also is codirector of the UAB Pharmacoepidemiology and Pharmacoeconomics Unit.
Additional physical health domains that PROs measure include dyspnea, gastrointestinal symptoms, pain behavior, pain quality, sexual function, and sleep-related impairment.
These are “things that, honestly, we don’t talk about much as a field, but absolutely affect patients with autoimmune diseases,” he said. “You know, sexual function – that doesn’t come up in my practice spontaneously very often, but there are ways you can quantify that, and for many patients that’s actually a big deal.”
The domains measured by PROMIS tools for mental health look at anxiety and depression, but also delve into alcohol use, anger, cognitive function, life satisfaction, self-efficacy for managing chronic conditions, substance use, and more. The domains for social health address ability to participate in social roles and activities, as well as companionship, satisfaction with social roles and activity, social isolation, and social support.
“You can’t go on a hike with friends [and] be far from a bathroom, because you have bad arthritis and you have Crohn’s disease. Well, that’s kind of an important thing that may or may not come up in your discussions about inflammatory arthritis associated with [inflammatory bowel disease],” he said.
Another example is a patient who is embarrassed attending social functions or wearing a swimsuit because of really bad psoriasis.
“These are the kinds of things that I’m suggesting you and I probably want to measure if we’re providing holistic care to rheumatology patients,” Dr. Curtis said.
The PROMIS tools provide a simple, user-friendly means for doing so in English, Spanish, and many other languages, he noted.
All the scales use the same 1-100 scoring range, which simplifies measurements. They are available for free by download and can be printed or used electronically for use in the office, at home, on the web, and via smartphone.
The NIH developed the PROMIS tools several years ago and validated them for multiple chronic disease populations, Dr. Curtis said, adding that the tools include multiple individual domains and overall “profiles” of varying lengths.
Most are fixed-length scales that are between 4 and 10 questions and can be completed within 30-60 seconds per scale, so several scales can be completed within 5-10 minutes.
However, some scales are longer and provide greater detail.
“The nice thing is that if you ask a few more questions you can get more precise information – there’s more of a floor and ceiling. You can detect people who do really well. You can distinguish between the marathon runners and the 5K-ers and the people who can walk 2 miles but aren’t going to run a race,” he explained.
Further, the PROMIS tools, like the 36-item Short Form Health Survey (SF-36), are benchmarked against the U.S. adult population, allowing for assessment of how a specific drug or treatment “impacts your arthritis patient on a scale that would also be relevant for somebody who doesn’t have arthritis, they have diabetes.”
The metrics and scales are the same, and that can be helpful when trying to get a payer to pay for a particular drug, he said.
“None of these are rheumatology specific; this puts PROs into a language that can help rheumatology contend for the value of the care that we provide on a scale that would be relevant for any other chronic illness, even for nonrheumatology patients,” he explained.
In addition, minimally important differences (group mean change of about 2-3 units) and minimally clinical important differences for individuals (5 units) have been established.
“So we know what the numbers mean, and this is true for all of the scales,” he said.
PROMIS tools also include computer-adaptive testing (CAT) versions, which helps to personalize the scales to provide more precise information for a given patient and eliminate irrelevant information.
Of note, PROMIS health measures are among the data that can be tracked on a smartphone using Arthritis Power, an arthritis research registry developed with the help of a recent infrastructure grant awarded to the Center for Education and Research and Therapeutics of Musculoskeletal Disorders at UAB, Dr. Curtis said.
The measures were also shown in the AWARE study to track closely with other measures, including the Clinical Disease Activity Index (CDAI), and with patient improvement on therapy.
“So these PROMIS scores are tracking with things that you and I are familiar with ... and it looks like these scores are faithfully tracking, over time, patients getting better on therapies that we would expect them to,” he said. “I think this is additional validation – not just from the National Institutes of Health and a decade of research by lots of different groups, but in our own field – that these actually correlate with disease activity ... and that when you start an effective therapy like a [tumor necrosis factor inhibitor] they’re going to improve as you would anticipate.”
Dr. Curtis reported funding from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the Patient-Centered Outcomes Research Institute. He has also consulted for or received research grants from Amgen, AbbVie, Bristol-Myers Squibb, CORRONA, Lilly, Janssen, Myriad, Novartis, Roche, Pfizer, and Sanofi/Regeneron.
EXPERT ANALYSIS FROM FSR 2019
PTSD in the inpatient setting
A problem hiding in plain sight
“I need to get out of here! I haven’t gotten any sleep, my medications never come on time, and I feel like a pincushion. I am leaving NOW!” The commotion interrupts your intern’s meticulous presentation as your team quickly files into the room. You find a disheveled, visibly frustrated man tearing at his intravenous line, surrounded by his half-eaten breakfast and multiple urinals filled to various levels. His IV pump is beeping, and telemetry wires hang haphazardly off his chest.
Mr. Smith had been admitted for a heart failure exacerbation. You’d been making steady progress with diuresis but are now faced with a likely discharge against medical advice if you can’t defuse the situation.
As hospitalists, this scenario might feel eerily familiar. Perhaps Mr. Smith had enough of being in the hospital and just wanted to go home to see his dog, or maybe the food was not up to his standards.
However, his next line stops your team dead in its tracks. “I feel like I am in Vietnam all over again. I am tied up with all these wires and feel like a prisoner! Please let me go.” It turns out that Mr. Smith had a comorbidity that was overlooked during his initial intake: posttraumatic stress disorder.
Impact of PTSD
PTSD is a diagnosis characterized by intrusive recurrent thoughts, dreams, or flashbacks that follow exposure to a traumatic event or series of events (see Table 1). While more common among veterans (for example, Vietnam veterans have an estimated lifetime prevalence of PTSD of 30.9% for men and 26.9% for women),1 a national survey of U.S. households estimated the lifetime prevalence of PTSD among adult Americans to be 6.8%.2 PTSD is often underdiagnosed and underreported by patients in the outpatient setting, leading to underrecognition and undertreatment of these patients in the inpatient setting.
Although it may not be surprising that patients with PTSD use more mental health services, they are also more likely to use nonmental health services. In one study, total utilization of outpatient nonmental health services was 91% greater in veterans with PTSD, and these patients were three times more likely to be hospitalized than those without any mental health diagnoses.3 Additionally, they are likely to present later and stay longer when compared with patients without PTSD. One study estimated the cost of PTSD-related hospitalization in the United States from 2002 to 2011 as being $34.9 billion.4 Notably, close to 95% of hospitalizations in this study listed PTSD as a secondary rather than primary diagnosis, suggesting that the vast majority of these admitted patients are cared for by frontline providers who are not trained mental health professionals.
How PTSD manifests in the hospital
But, how exactly can the hospital environment contribute to decompensation of PTSD symptoms? Unfortunately, there is little empiric data to guide us. Based on what we do know of PTSD, we offer the following hypotheses.
Patients with PTSD may feel a loss of control or helplessness when admitted to the inpatient setting. For example, they cannot control when they receive their medications or when they get their meals. The act of showering or going outside requires approval. In addition, they might perceive they are being “ordered around” by staff and may be carted off to a study without knowing why the study is being done in the first place.
Triggers in the hospital environment may contribute to PTSD flares. Think about the loud, beeping IV pump that constantly goes off at random intervals, disrupting sleep. What about a blood draw in the early morning where the phlebotomist sticks a needle into the arm of a sleeping patient? Or the well-intentioned provider doing prerounds who wakes a sleeping patient with a shake of the shoulder or some other form of physical touch? The multidisciplinary team crowding around their hospital bed? For a patient suffering from PTSD, any of these could easily set off a cascade of escalating symptoms.
Knowing that these triggers exist, can anything be done to ameliorate their effects? We propose some practical suggestions for improving the hospital experience for patients with PTSD.
Strategies to combat PTSD in the inpatient setting
Perhaps the most practical place to start is with preserving sleep in hospitalized patients with PTSD. The majority of patients with PTSD have sleep disturbances, and interrupted sleep routines in these patients can exacerbate nightmares and underlying psychiatric issues.5 Therefore, we should strive to avoid unnecessary awakenings.
While this principle holds true for all hospitalized patients, it must be especially prioritized in patients with PTSD. Ask yourself these questions during your next admission: Must intravenous fluids run 24 hours a day, or could they be stopped at 6 p.m.? Are vital signs needed overnight? Could the last dose of furosemide occur at 4 p.m. to avoid nocturia?
Another strategy involves bedtime routines. Many of these patients may already follow a home sleep routine as part of their chronic PTSD management. To honor these habits in the hospital might mean that staff encourage turning the lights and the television off at a designated time. Additionally, the literature suggests music therapy can have a significant impact on enhanced sleep quality. When available, music therapy may reduce insomnia and decrease the amount of time prior to falling asleep.6
Other methods to counteract PTSD fall under the general principle of “trauma-informed care.” Trauma-informed care comprises practices promoting a culture of safety, empowerment, and healing.7 It is a mindful and sensitive approach that acknowledges the pervasive nature of trauma exposure, the reality of ongoing adverse effects in trauma survivors, and the fact that recovery is highly personal and complex.8
By definition, patients with PTSD have endured some traumatic event. Therefore, ideal care teams will ask patients about things that may trigger their anxiety and then work to mitigate them. For example, some patients with PTSD have a severe startle response when woken up by someone touching them. When patients feel that they can share their concerns with their care team and their team honors that observation by waking them in a different way, trust and control may be gained. This process of asking for patient guidance and adjusting accordingly is consistent with a trauma-informed care approach.9 A true trauma-informed care approach involves the entire practice environment but examining and adjusting our own behavior and assumptions are good places to start.
Summary of recommended treatments
Psychotherapy is preferable over pharmacotherapy, but both can be combined as needed. Individual trauma-focused psychotherapies utilizing a primary component of exposure and/or cognitive restructuring have strong evidence for effectiveness but are primarily outpatient based.
For pharmacologic treatment, selective serotonin reuptake inhibitors (for example, sertraline, paroxetine, or fluoxetine) and serotonin norepinephrine reuptake inhibitors (for example, venlafaxine) monotherapy have strong evidence for effectiveness and can be started while inpatient. However, these medications typically take weeks to produce benefits. Recent trials studying prazosin, an alpha1-adrenergic receptor antagonist used to alleviate nightmares associated with PTSD, have demonstrated inefficacy or even harm,leading experts to caution against its use.10,11 Finally, benzodiazepine and atypical antipsychotic usage should be restricted and used as a last resort.12
In summary, PTSD is common among veterans and nonveterans. While hospitalists may rarely admit patients because of their PTSD, they will often take care of patients who have PTSD as a comorbidity. Therefore, understanding the basics of PTSD and how hospitalization may exacerbate its symptoms can meaningfully improve care for these patients.
Dr. Fletcher is a hospitalist at the Milwaukee Veterans Affairs Medical Center and Froedtert Hospital in Wauwatosa, Wis. She is professor of internal medicine and program director for the internal medicine residency program at the Medical College of Wisconsin, Milwaukee. She is also faculty mentor for the VA’s Chief Resident for Quality and Safety. Dr. Kwan is a hospitalist at the VA San Diego Healthcare System and is associate professor at the University of California, San Diego, in the division of hospital medicine. He serves as an associate clerkship director of both the internal medicine clerkship and the medicine subinternship. He is the chair of SHM’s Physicians in Training committee. Dr. Steinbach is chief of hospital medicine at the Atlanta VA Medical Center and assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.
References
1. Kang HK et al. Posttraumatic stress disorder and chronic fatigue syndrome–like illness among Gulf War veterans: A population-based survey of 30,000 veterans. Am J Epidemiol. 2003;157(2):141-8.
2. Kessler RC et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005; 62(6):593-602.
3. Cohen BE et al. Mental health diagnoses and utilization of VA nonmental health medical services among returning Iraq and Afghanistan veterans. J Gen Intern Med. 2010;25(1):18-24.
4. Haviland MG et al. Posttraumatic stress disorder–related hospitalizations in the United States (2002-2011): Rates, co-occurring illnesses, suicidal ideation/self-harm, and hospital charges. J Nerv Ment Dis. 2016; 204(2):78-86.
5. Aurora RN et al. Best practice guide for the treatment of nightmare disorder in adults. J Clin Sleep Med. 2010;6(4):389-401.
6. Blanaru M et al. The effects of music relaxation and muscle relaxation techniques on sleep quality and emotional measures among individuals with posttraumatic stress disorder. Ment Illn. 2012;4(2):e13.
7. Tello M. (2018, Oct 16). Trauma-informed care: What it is, and why it’s important. Retrieved March 18, 2019, from https://www.health.harvard.edu/blog/trauma-informed-care-what-it-is-and-why-its-important-2018101613562.
8. Harris M et al. Using trauma theory to design service systems. San Francisco: 2001.
9. Substance abuse and mental health services administration. SAMHSA’s concept of trauma and guidance for a trauma-informed approach. HHS publication no. SMA 14-4884. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2014.
10. Raskind MA et al. Trial of prazosin for posttraumatic stress disorder in military veterans. N Engl J Med. 2018 Feb 8;378(6):507-7.
11. McCall WV et al. A pilot, randomized clinical trial of bedtime doses of prazosin versus placebo in suicidal posttraumatic stress disorder patients with nightmares. J Clin Psychopharmacol. 2018 Dec;38(6):618-21.
12. U.S. Department of Veterans Affairs/U.S. Department of Defense. Clinical practice guideline for the management of posttraumatic stress disorder and acute stress reaction 2017. Accessed February 18, 2019.
A problem hiding in plain sight
A problem hiding in plain sight
“I need to get out of here! I haven’t gotten any sleep, my medications never come on time, and I feel like a pincushion. I am leaving NOW!” The commotion interrupts your intern’s meticulous presentation as your team quickly files into the room. You find a disheveled, visibly frustrated man tearing at his intravenous line, surrounded by his half-eaten breakfast and multiple urinals filled to various levels. His IV pump is beeping, and telemetry wires hang haphazardly off his chest.
Mr. Smith had been admitted for a heart failure exacerbation. You’d been making steady progress with diuresis but are now faced with a likely discharge against medical advice if you can’t defuse the situation.
As hospitalists, this scenario might feel eerily familiar. Perhaps Mr. Smith had enough of being in the hospital and just wanted to go home to see his dog, or maybe the food was not up to his standards.
However, his next line stops your team dead in its tracks. “I feel like I am in Vietnam all over again. I am tied up with all these wires and feel like a prisoner! Please let me go.” It turns out that Mr. Smith had a comorbidity that was overlooked during his initial intake: posttraumatic stress disorder.
Impact of PTSD
PTSD is a diagnosis characterized by intrusive recurrent thoughts, dreams, or flashbacks that follow exposure to a traumatic event or series of events (see Table 1). While more common among veterans (for example, Vietnam veterans have an estimated lifetime prevalence of PTSD of 30.9% for men and 26.9% for women),1 a national survey of U.S. households estimated the lifetime prevalence of PTSD among adult Americans to be 6.8%.2 PTSD is often underdiagnosed and underreported by patients in the outpatient setting, leading to underrecognition and undertreatment of these patients in the inpatient setting.
Although it may not be surprising that patients with PTSD use more mental health services, they are also more likely to use nonmental health services. In one study, total utilization of outpatient nonmental health services was 91% greater in veterans with PTSD, and these patients were three times more likely to be hospitalized than those without any mental health diagnoses.3 Additionally, they are likely to present later and stay longer when compared with patients without PTSD. One study estimated the cost of PTSD-related hospitalization in the United States from 2002 to 2011 as being $34.9 billion.4 Notably, close to 95% of hospitalizations in this study listed PTSD as a secondary rather than primary diagnosis, suggesting that the vast majority of these admitted patients are cared for by frontline providers who are not trained mental health professionals.
How PTSD manifests in the hospital
But, how exactly can the hospital environment contribute to decompensation of PTSD symptoms? Unfortunately, there is little empiric data to guide us. Based on what we do know of PTSD, we offer the following hypotheses.
Patients with PTSD may feel a loss of control or helplessness when admitted to the inpatient setting. For example, they cannot control when they receive their medications or when they get their meals. The act of showering or going outside requires approval. In addition, they might perceive they are being “ordered around” by staff and may be carted off to a study without knowing why the study is being done in the first place.
Triggers in the hospital environment may contribute to PTSD flares. Think about the loud, beeping IV pump that constantly goes off at random intervals, disrupting sleep. What about a blood draw in the early morning where the phlebotomist sticks a needle into the arm of a sleeping patient? Or the well-intentioned provider doing prerounds who wakes a sleeping patient with a shake of the shoulder or some other form of physical touch? The multidisciplinary team crowding around their hospital bed? For a patient suffering from PTSD, any of these could easily set off a cascade of escalating symptoms.
Knowing that these triggers exist, can anything be done to ameliorate their effects? We propose some practical suggestions for improving the hospital experience for patients with PTSD.
Strategies to combat PTSD in the inpatient setting
Perhaps the most practical place to start is with preserving sleep in hospitalized patients with PTSD. The majority of patients with PTSD have sleep disturbances, and interrupted sleep routines in these patients can exacerbate nightmares and underlying psychiatric issues.5 Therefore, we should strive to avoid unnecessary awakenings.
While this principle holds true for all hospitalized patients, it must be especially prioritized in patients with PTSD. Ask yourself these questions during your next admission: Must intravenous fluids run 24 hours a day, or could they be stopped at 6 p.m.? Are vital signs needed overnight? Could the last dose of furosemide occur at 4 p.m. to avoid nocturia?
Another strategy involves bedtime routines. Many of these patients may already follow a home sleep routine as part of their chronic PTSD management. To honor these habits in the hospital might mean that staff encourage turning the lights and the television off at a designated time. Additionally, the literature suggests music therapy can have a significant impact on enhanced sleep quality. When available, music therapy may reduce insomnia and decrease the amount of time prior to falling asleep.6
Other methods to counteract PTSD fall under the general principle of “trauma-informed care.” Trauma-informed care comprises practices promoting a culture of safety, empowerment, and healing.7 It is a mindful and sensitive approach that acknowledges the pervasive nature of trauma exposure, the reality of ongoing adverse effects in trauma survivors, and the fact that recovery is highly personal and complex.8
By definition, patients with PTSD have endured some traumatic event. Therefore, ideal care teams will ask patients about things that may trigger their anxiety and then work to mitigate them. For example, some patients with PTSD have a severe startle response when woken up by someone touching them. When patients feel that they can share their concerns with their care team and their team honors that observation by waking them in a different way, trust and control may be gained. This process of asking for patient guidance and adjusting accordingly is consistent with a trauma-informed care approach.9 A true trauma-informed care approach involves the entire practice environment but examining and adjusting our own behavior and assumptions are good places to start.
Summary of recommended treatments
Psychotherapy is preferable over pharmacotherapy, but both can be combined as needed. Individual trauma-focused psychotherapies utilizing a primary component of exposure and/or cognitive restructuring have strong evidence for effectiveness but are primarily outpatient based.
For pharmacologic treatment, selective serotonin reuptake inhibitors (for example, sertraline, paroxetine, or fluoxetine) and serotonin norepinephrine reuptake inhibitors (for example, venlafaxine) monotherapy have strong evidence for effectiveness and can be started while inpatient. However, these medications typically take weeks to produce benefits. Recent trials studying prazosin, an alpha1-adrenergic receptor antagonist used to alleviate nightmares associated with PTSD, have demonstrated inefficacy or even harm,leading experts to caution against its use.10,11 Finally, benzodiazepine and atypical antipsychotic usage should be restricted and used as a last resort.12
In summary, PTSD is common among veterans and nonveterans. While hospitalists may rarely admit patients because of their PTSD, they will often take care of patients who have PTSD as a comorbidity. Therefore, understanding the basics of PTSD and how hospitalization may exacerbate its symptoms can meaningfully improve care for these patients.
Dr. Fletcher is a hospitalist at the Milwaukee Veterans Affairs Medical Center and Froedtert Hospital in Wauwatosa, Wis. She is professor of internal medicine and program director for the internal medicine residency program at the Medical College of Wisconsin, Milwaukee. She is also faculty mentor for the VA’s Chief Resident for Quality and Safety. Dr. Kwan is a hospitalist at the VA San Diego Healthcare System and is associate professor at the University of California, San Diego, in the division of hospital medicine. He serves as an associate clerkship director of both the internal medicine clerkship and the medicine subinternship. He is the chair of SHM’s Physicians in Training committee. Dr. Steinbach is chief of hospital medicine at the Atlanta VA Medical Center and assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.
References
1. Kang HK et al. Posttraumatic stress disorder and chronic fatigue syndrome–like illness among Gulf War veterans: A population-based survey of 30,000 veterans. Am J Epidemiol. 2003;157(2):141-8.
2. Kessler RC et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005; 62(6):593-602.
3. Cohen BE et al. Mental health diagnoses and utilization of VA nonmental health medical services among returning Iraq and Afghanistan veterans. J Gen Intern Med. 2010;25(1):18-24.
4. Haviland MG et al. Posttraumatic stress disorder–related hospitalizations in the United States (2002-2011): Rates, co-occurring illnesses, suicidal ideation/self-harm, and hospital charges. J Nerv Ment Dis. 2016; 204(2):78-86.
5. Aurora RN et al. Best practice guide for the treatment of nightmare disorder in adults. J Clin Sleep Med. 2010;6(4):389-401.
6. Blanaru M et al. The effects of music relaxation and muscle relaxation techniques on sleep quality and emotional measures among individuals with posttraumatic stress disorder. Ment Illn. 2012;4(2):e13.
7. Tello M. (2018, Oct 16). Trauma-informed care: What it is, and why it’s important. Retrieved March 18, 2019, from https://www.health.harvard.edu/blog/trauma-informed-care-what-it-is-and-why-its-important-2018101613562.
8. Harris M et al. Using trauma theory to design service systems. San Francisco: 2001.
9. Substance abuse and mental health services administration. SAMHSA’s concept of trauma and guidance for a trauma-informed approach. HHS publication no. SMA 14-4884. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2014.
10. Raskind MA et al. Trial of prazosin for posttraumatic stress disorder in military veterans. N Engl J Med. 2018 Feb 8;378(6):507-7.
11. McCall WV et al. A pilot, randomized clinical trial of bedtime doses of prazosin versus placebo in suicidal posttraumatic stress disorder patients with nightmares. J Clin Psychopharmacol. 2018 Dec;38(6):618-21.
12. U.S. Department of Veterans Affairs/U.S. Department of Defense. Clinical practice guideline for the management of posttraumatic stress disorder and acute stress reaction 2017. Accessed February 18, 2019.
“I need to get out of here! I haven’t gotten any sleep, my medications never come on time, and I feel like a pincushion. I am leaving NOW!” The commotion interrupts your intern’s meticulous presentation as your team quickly files into the room. You find a disheveled, visibly frustrated man tearing at his intravenous line, surrounded by his half-eaten breakfast and multiple urinals filled to various levels. His IV pump is beeping, and telemetry wires hang haphazardly off his chest.
Mr. Smith had been admitted for a heart failure exacerbation. You’d been making steady progress with diuresis but are now faced with a likely discharge against medical advice if you can’t defuse the situation.
As hospitalists, this scenario might feel eerily familiar. Perhaps Mr. Smith had enough of being in the hospital and just wanted to go home to see his dog, or maybe the food was not up to his standards.
However, his next line stops your team dead in its tracks. “I feel like I am in Vietnam all over again. I am tied up with all these wires and feel like a prisoner! Please let me go.” It turns out that Mr. Smith had a comorbidity that was overlooked during his initial intake: posttraumatic stress disorder.
Impact of PTSD
PTSD is a diagnosis characterized by intrusive recurrent thoughts, dreams, or flashbacks that follow exposure to a traumatic event or series of events (see Table 1). While more common among veterans (for example, Vietnam veterans have an estimated lifetime prevalence of PTSD of 30.9% for men and 26.9% for women),1 a national survey of U.S. households estimated the lifetime prevalence of PTSD among adult Americans to be 6.8%.2 PTSD is often underdiagnosed and underreported by patients in the outpatient setting, leading to underrecognition and undertreatment of these patients in the inpatient setting.
Although it may not be surprising that patients with PTSD use more mental health services, they are also more likely to use nonmental health services. In one study, total utilization of outpatient nonmental health services was 91% greater in veterans with PTSD, and these patients were three times more likely to be hospitalized than those without any mental health diagnoses.3 Additionally, they are likely to present later and stay longer when compared with patients without PTSD. One study estimated the cost of PTSD-related hospitalization in the United States from 2002 to 2011 as being $34.9 billion.4 Notably, close to 95% of hospitalizations in this study listed PTSD as a secondary rather than primary diagnosis, suggesting that the vast majority of these admitted patients are cared for by frontline providers who are not trained mental health professionals.
How PTSD manifests in the hospital
But, how exactly can the hospital environment contribute to decompensation of PTSD symptoms? Unfortunately, there is little empiric data to guide us. Based on what we do know of PTSD, we offer the following hypotheses.
Patients with PTSD may feel a loss of control or helplessness when admitted to the inpatient setting. For example, they cannot control when they receive their medications or when they get their meals. The act of showering or going outside requires approval. In addition, they might perceive they are being “ordered around” by staff and may be carted off to a study without knowing why the study is being done in the first place.
Triggers in the hospital environment may contribute to PTSD flares. Think about the loud, beeping IV pump that constantly goes off at random intervals, disrupting sleep. What about a blood draw in the early morning where the phlebotomist sticks a needle into the arm of a sleeping patient? Or the well-intentioned provider doing prerounds who wakes a sleeping patient with a shake of the shoulder or some other form of physical touch? The multidisciplinary team crowding around their hospital bed? For a patient suffering from PTSD, any of these could easily set off a cascade of escalating symptoms.
Knowing that these triggers exist, can anything be done to ameliorate their effects? We propose some practical suggestions for improving the hospital experience for patients with PTSD.
Strategies to combat PTSD in the inpatient setting
Perhaps the most practical place to start is with preserving sleep in hospitalized patients with PTSD. The majority of patients with PTSD have sleep disturbances, and interrupted sleep routines in these patients can exacerbate nightmares and underlying psychiatric issues.5 Therefore, we should strive to avoid unnecessary awakenings.
While this principle holds true for all hospitalized patients, it must be especially prioritized in patients with PTSD. Ask yourself these questions during your next admission: Must intravenous fluids run 24 hours a day, or could they be stopped at 6 p.m.? Are vital signs needed overnight? Could the last dose of furosemide occur at 4 p.m. to avoid nocturia?
Another strategy involves bedtime routines. Many of these patients may already follow a home sleep routine as part of their chronic PTSD management. To honor these habits in the hospital might mean that staff encourage turning the lights and the television off at a designated time. Additionally, the literature suggests music therapy can have a significant impact on enhanced sleep quality. When available, music therapy may reduce insomnia and decrease the amount of time prior to falling asleep.6
Other methods to counteract PTSD fall under the general principle of “trauma-informed care.” Trauma-informed care comprises practices promoting a culture of safety, empowerment, and healing.7 It is a mindful and sensitive approach that acknowledges the pervasive nature of trauma exposure, the reality of ongoing adverse effects in trauma survivors, and the fact that recovery is highly personal and complex.8
By definition, patients with PTSD have endured some traumatic event. Therefore, ideal care teams will ask patients about things that may trigger their anxiety and then work to mitigate them. For example, some patients with PTSD have a severe startle response when woken up by someone touching them. When patients feel that they can share their concerns with their care team and their team honors that observation by waking them in a different way, trust and control may be gained. This process of asking for patient guidance and adjusting accordingly is consistent with a trauma-informed care approach.9 A true trauma-informed care approach involves the entire practice environment but examining and adjusting our own behavior and assumptions are good places to start.
Summary of recommended treatments
Psychotherapy is preferable over pharmacotherapy, but both can be combined as needed. Individual trauma-focused psychotherapies utilizing a primary component of exposure and/or cognitive restructuring have strong evidence for effectiveness but are primarily outpatient based.
For pharmacologic treatment, selective serotonin reuptake inhibitors (for example, sertraline, paroxetine, or fluoxetine) and serotonin norepinephrine reuptake inhibitors (for example, venlafaxine) monotherapy have strong evidence for effectiveness and can be started while inpatient. However, these medications typically take weeks to produce benefits. Recent trials studying prazosin, an alpha1-adrenergic receptor antagonist used to alleviate nightmares associated with PTSD, have demonstrated inefficacy or even harm,leading experts to caution against its use.10,11 Finally, benzodiazepine and atypical antipsychotic usage should be restricted and used as a last resort.12
In summary, PTSD is common among veterans and nonveterans. While hospitalists may rarely admit patients because of their PTSD, they will often take care of patients who have PTSD as a comorbidity. Therefore, understanding the basics of PTSD and how hospitalization may exacerbate its symptoms can meaningfully improve care for these patients.
Dr. Fletcher is a hospitalist at the Milwaukee Veterans Affairs Medical Center and Froedtert Hospital in Wauwatosa, Wis. She is professor of internal medicine and program director for the internal medicine residency program at the Medical College of Wisconsin, Milwaukee. She is also faculty mentor for the VA’s Chief Resident for Quality and Safety. Dr. Kwan is a hospitalist at the VA San Diego Healthcare System and is associate professor at the University of California, San Diego, in the division of hospital medicine. He serves as an associate clerkship director of both the internal medicine clerkship and the medicine subinternship. He is the chair of SHM’s Physicians in Training committee. Dr. Steinbach is chief of hospital medicine at the Atlanta VA Medical Center and assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta.
References
1. Kang HK et al. Posttraumatic stress disorder and chronic fatigue syndrome–like illness among Gulf War veterans: A population-based survey of 30,000 veterans. Am J Epidemiol. 2003;157(2):141-8.
2. Kessler RC et al. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005; 62(6):593-602.
3. Cohen BE et al. Mental health diagnoses and utilization of VA nonmental health medical services among returning Iraq and Afghanistan veterans. J Gen Intern Med. 2010;25(1):18-24.
4. Haviland MG et al. Posttraumatic stress disorder–related hospitalizations in the United States (2002-2011): Rates, co-occurring illnesses, suicidal ideation/self-harm, and hospital charges. J Nerv Ment Dis. 2016; 204(2):78-86.
5. Aurora RN et al. Best practice guide for the treatment of nightmare disorder in adults. J Clin Sleep Med. 2010;6(4):389-401.
6. Blanaru M et al. The effects of music relaxation and muscle relaxation techniques on sleep quality and emotional measures among individuals with posttraumatic stress disorder. Ment Illn. 2012;4(2):e13.
7. Tello M. (2018, Oct 16). Trauma-informed care: What it is, and why it’s important. Retrieved March 18, 2019, from https://www.health.harvard.edu/blog/trauma-informed-care-what-it-is-and-why-its-important-2018101613562.
8. Harris M et al. Using trauma theory to design service systems. San Francisco: 2001.
9. Substance abuse and mental health services administration. SAMHSA’s concept of trauma and guidance for a trauma-informed approach. HHS publication no. SMA 14-4884. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2014.
10. Raskind MA et al. Trial of prazosin for posttraumatic stress disorder in military veterans. N Engl J Med. 2018 Feb 8;378(6):507-7.
11. McCall WV et al. A pilot, randomized clinical trial of bedtime doses of prazosin versus placebo in suicidal posttraumatic stress disorder patients with nightmares. J Clin Psychopharmacol. 2018 Dec;38(6):618-21.
12. U.S. Department of Veterans Affairs/U.S. Department of Defense. Clinical practice guideline for the management of posttraumatic stress disorder and acute stress reaction 2017. Accessed February 18, 2019.
Apply for SVS Membership
The third membership deadline of 2019 is less than one month away on Sept. 1. SVS members enjoy many benefits such as SVSConnect, discounted pricing on publications and meeting registration, practice management resources and much more. Visit the membership page and start your application today. If you have any questions, please contact the SVS membership department at [email protected].
The third membership deadline of 2019 is less than one month away on Sept. 1. SVS members enjoy many benefits such as SVSConnect, discounted pricing on publications and meeting registration, practice management resources and much more. Visit the membership page and start your application today. If you have any questions, please contact the SVS membership department at [email protected].
The third membership deadline of 2019 is less than one month away on Sept. 1. SVS members enjoy many benefits such as SVSConnect, discounted pricing on publications and meeting registration, practice management resources and much more. Visit the membership page and start your application today. If you have any questions, please contact the SVS membership department at [email protected].
Staying Awake to Evade Death
ANSWER
The correct answer includes sinus rhythm with second-degree atrioventricular (AV) block (Mobitz I) and a right bundle branch block (RBBB).
Sinus rhythm is evidenced by the consistent P-P intervals (best measured in the lead I rhythm strip). Mobitz I block is distinguished from Mobitz II block by the varying PR interval.
Remember that in Mobitz I (Wenckebach) block, the PR interval becomes progressively longer as the AV node fatigues, until there is blocked conduction between the atria and ventricles resulting in a P wave with no associated QRS complex. This is evident in the pause between the 6th and 7th QRS complexes. Notice also that the very next PR interval following the dropped QRS complex is much shorter than the PR interval immediately prior to that complex. In this example, the increasing PR interval before the pause is subtle compared to the PR intervals following the pause.
The skipped beats the patient feels are these pauses. Increased parasympathetic (vagal) activity occurs when a person is falling asleep, resulting in a reduction in heart rate and AV nodal conduction variability.
Finally, don’t forget the RBBB. It is indicated by a QRS duration > 120 ms, rSR’ complexes in precordial leads V1 to V3, and slurred S waves in leads I and aVF.
ANSWER
The correct answer includes sinus rhythm with second-degree atrioventricular (AV) block (Mobitz I) and a right bundle branch block (RBBB).
Sinus rhythm is evidenced by the consistent P-P intervals (best measured in the lead I rhythm strip). Mobitz I block is distinguished from Mobitz II block by the varying PR interval.
Remember that in Mobitz I (Wenckebach) block, the PR interval becomes progressively longer as the AV node fatigues, until there is blocked conduction between the atria and ventricles resulting in a P wave with no associated QRS complex. This is evident in the pause between the 6th and 7th QRS complexes. Notice also that the very next PR interval following the dropped QRS complex is much shorter than the PR interval immediately prior to that complex. In this example, the increasing PR interval before the pause is subtle compared to the PR intervals following the pause.
The skipped beats the patient feels are these pauses. Increased parasympathetic (vagal) activity occurs when a person is falling asleep, resulting in a reduction in heart rate and AV nodal conduction variability.
Finally, don’t forget the RBBB. It is indicated by a QRS duration > 120 ms, rSR’ complexes in precordial leads V1 to V3, and slurred S waves in leads I and aVF.
ANSWER
The correct answer includes sinus rhythm with second-degree atrioventricular (AV) block (Mobitz I) and a right bundle branch block (RBBB).
Sinus rhythm is evidenced by the consistent P-P intervals (best measured in the lead I rhythm strip). Mobitz I block is distinguished from Mobitz II block by the varying PR interval.
Remember that in Mobitz I (Wenckebach) block, the PR interval becomes progressively longer as the AV node fatigues, until there is blocked conduction between the atria and ventricles resulting in a P wave with no associated QRS complex. This is evident in the pause between the 6th and 7th QRS complexes. Notice also that the very next PR interval following the dropped QRS complex is much shorter than the PR interval immediately prior to that complex. In this example, the increasing PR interval before the pause is subtle compared to the PR intervals following the pause.
The skipped beats the patient feels are these pauses. Increased parasympathetic (vagal) activity occurs when a person is falling asleep, resulting in a reduction in heart rate and AV nodal conduction variability.
Finally, don’t forget the RBBB. It is indicated by a QRS duration > 120 ms, rSR’ complexes in precordial leads V1 to V3, and slurred S waves in leads I and aVF.
A 64-year-old man presents with a 6-month history of skipped heart beats. He says this occurs most often in the evenings, when he’s resting, and he has been awakened by it. He denies chest pain, dyspnea with exertion, syncope, or near-syncope. He has been otherwise asymptomatic from a cardiac and pulmonary standpoint.
However, he is increasingly concerned that his heart may “just stop beating” when he is asleep. When pressed further, he reveals he is afraid to go to sleep at night, knowing “my heart will start skipping beats and I’ll die!” He has discussed his fear of dying in his sleep with a psychologist, who told him that although he experiences fatigue and loss of energy and has recurrent thoughts of death, he does not meet DSM-5 criteria for major depressive disorder. The psychologist obtained an ECG and noticed pauses, which prompted referral of the patient to you.
Past medical history is remarkable for hypertension, cirrhosis, and osteoarthritis. Surgical history includes bilateral knee and left hip replacements. A screening colonoscopy 1 month ago yielded a diagnosis of stage 1 colorectal cancer.
The patient’s medication list includes hydrochlorothiazide and celecoxib. He is allergic to oxycodone (anaphylaxis).
The patient is divorced, which he attributes to his ongoing alcoholism. He drinks half a bottle of whiskey daily to “help with my nerves” and “get drunk enough to sleep.” He reports a lifetime of heavy drinking; he has tried Alcoholics Anonymous but kept dropping out to drink. He also smokes up to 1.5 packs/d of cigarettes. He has no children. He worked as a machinist in a factory but was laid off a year ago when the company downsized.
Family history is positive for alcoholism (father, 2 brothers) and hypothyroidism (mother).
Review of systems is positive for a chronic smoker’s cough, lower abdominal cramping following his colonoscopy, and arthritic pain in his wrists and ankles.
Vital signs include a blood pressure of 174/92 mm Hg; pulse, 74 beats/min; respiratory rate, 14 breaths/min; and O2 saturation, 97% on room air. His weight is 247 lb and his height, 69 in. His BMI is 36.5.
Physical exam reveals a somewhat disheveled male in no apparent distress. He wears corrective lenses and has tobacco stains on his mustache. His HEENT exam is surprisingly normal, and there is no evidence of rhinophyma. There is no jugular venous distention, thyromegaly, or lymphadenopathy. There are crackles and late expiratory wheezes in both lower lung fields.
The cardiac exam reveals a regular rate and rhythm of 74 beats/min, with no murmurs, rubs, or extra heart sounds. Peripheral pulses are strong and equal bilaterally. The abdomen is obese but nontender, and there are no palpable masses. There are surgical scars over both knees and the left hip. Arthritic changes are noticeable in the fingers on both hands. There are no neurologic deficits.
Through the electronic medical record, you access the ECG taken in the psychologist’s office. It shows a ventricular rate of 56 beats/min; no measurable PR interval; QRS duration, 144 ms; QT/QTc interval, 438/422 ms; P axis, 47°; R axis, –24°; and T axis, 55°. What is your interpretation of this ECG?
State and federal efforts address rheumatology workforce issues
LAKE BUENA VISTA, FLA. – Workforce gaps loom large in rheumatology, but efforts on both the federal and state levels address the problem, according to the chair of the American College of Rheumatology’s Government Affairs Committee, Angus B. Worthing, MD.
“We have a workforce gap that’s growing in adult arthritis; demand is increasing, and supply is decreasing,” Dr. Worthing said during an update on the committee’s activities at the annual meeting of the Florida Society of Rheumatology.
A similar “grave discrepancy” plagues pediatric rheumatology, said Dr. Worthing, a partner in a private rheumatology practice in the Washington, D.C., area.
“But these are fundamentally different,” he said, explaining that there is an oversupply of applicants for adult rheumatology fellowship spots, whereas only half of the available spots in pediatric rheumatology are being filled.
“We’re unfortunately having to turn away highly qualified [adult rheumatology] applicants, because we don’t have enough money to fund fellowship positions in the United States; about 100 doctors a year who wanted to be rheumatologists are going into other specialties,” he said. “It’s a different problem in pediatric rheumatology where you spend 2-3 extra years to earn less money than you would as a general pediatrician.”
The American College of Rheumatology is working to “find those dollars,” to alleviate the problems, he said, encouraging those who are concerned about the workforce issues to consider investing in the Rheumatology Research Foundation, which is a “huge supporter of rheumatology fellowships.”
Another proposal involves loan repayment plans for health professionals who agree to work at least 2 years in pediatric medicine.
“There’s an active bill that you can send an e-mail on right now,” Dr. Worthing said.
The bill, titled the “Educating Medical Professionals and Optimizing Workforce Efficiency and Readiness [EMPOWER] for Health Act,” represents an effort on the federal level to increase access to pediatric medical subspecialists by increasing the number who practice in underserved areas.
“It was introduced the day after we spoke on the Hill in May to leaders about this [issue],” he said.
Another effort is underway in Georgia, where a legislator who has lupus is working with the ACR on legislation that would allow the state to repay up to $25,000 on loans for cognitive specialists who agree to work in the state for a period of time.
The ACR is also working to maintain Deferred Action for Childhood Arrivals (DACA) protections for recipients pursuing medical education, who could potentially help to alleviate the shortages, he noted.
The problem of workforce issues is multifaceted and it requires a multipronged approach, Dr. Worthing said.
“It will not be solved by the American College of Rheumatology alone; I think it will end up being solved by people on the ground working with their primary care physicians and referring doctors to try to close the gap and try to see patients when they’re needed,” he said.
Dr. Worthing reported having no disclosures.
LAKE BUENA VISTA, FLA. – Workforce gaps loom large in rheumatology, but efforts on both the federal and state levels address the problem, according to the chair of the American College of Rheumatology’s Government Affairs Committee, Angus B. Worthing, MD.
“We have a workforce gap that’s growing in adult arthritis; demand is increasing, and supply is decreasing,” Dr. Worthing said during an update on the committee’s activities at the annual meeting of the Florida Society of Rheumatology.
A similar “grave discrepancy” plagues pediatric rheumatology, said Dr. Worthing, a partner in a private rheumatology practice in the Washington, D.C., area.
“But these are fundamentally different,” he said, explaining that there is an oversupply of applicants for adult rheumatology fellowship spots, whereas only half of the available spots in pediatric rheumatology are being filled.
“We’re unfortunately having to turn away highly qualified [adult rheumatology] applicants, because we don’t have enough money to fund fellowship positions in the United States; about 100 doctors a year who wanted to be rheumatologists are going into other specialties,” he said. “It’s a different problem in pediatric rheumatology where you spend 2-3 extra years to earn less money than you would as a general pediatrician.”
The American College of Rheumatology is working to “find those dollars,” to alleviate the problems, he said, encouraging those who are concerned about the workforce issues to consider investing in the Rheumatology Research Foundation, which is a “huge supporter of rheumatology fellowships.”
Another proposal involves loan repayment plans for health professionals who agree to work at least 2 years in pediatric medicine.
“There’s an active bill that you can send an e-mail on right now,” Dr. Worthing said.
The bill, titled the “Educating Medical Professionals and Optimizing Workforce Efficiency and Readiness [EMPOWER] for Health Act,” represents an effort on the federal level to increase access to pediatric medical subspecialists by increasing the number who practice in underserved areas.
“It was introduced the day after we spoke on the Hill in May to leaders about this [issue],” he said.
Another effort is underway in Georgia, where a legislator who has lupus is working with the ACR on legislation that would allow the state to repay up to $25,000 on loans for cognitive specialists who agree to work in the state for a period of time.
The ACR is also working to maintain Deferred Action for Childhood Arrivals (DACA) protections for recipients pursuing medical education, who could potentially help to alleviate the shortages, he noted.
The problem of workforce issues is multifaceted and it requires a multipronged approach, Dr. Worthing said.
“It will not be solved by the American College of Rheumatology alone; I think it will end up being solved by people on the ground working with their primary care physicians and referring doctors to try to close the gap and try to see patients when they’re needed,” he said.
Dr. Worthing reported having no disclosures.
LAKE BUENA VISTA, FLA. – Workforce gaps loom large in rheumatology, but efforts on both the federal and state levels address the problem, according to the chair of the American College of Rheumatology’s Government Affairs Committee, Angus B. Worthing, MD.
“We have a workforce gap that’s growing in adult arthritis; demand is increasing, and supply is decreasing,” Dr. Worthing said during an update on the committee’s activities at the annual meeting of the Florida Society of Rheumatology.
A similar “grave discrepancy” plagues pediatric rheumatology, said Dr. Worthing, a partner in a private rheumatology practice in the Washington, D.C., area.
“But these are fundamentally different,” he said, explaining that there is an oversupply of applicants for adult rheumatology fellowship spots, whereas only half of the available spots in pediatric rheumatology are being filled.
“We’re unfortunately having to turn away highly qualified [adult rheumatology] applicants, because we don’t have enough money to fund fellowship positions in the United States; about 100 doctors a year who wanted to be rheumatologists are going into other specialties,” he said. “It’s a different problem in pediatric rheumatology where you spend 2-3 extra years to earn less money than you would as a general pediatrician.”
The American College of Rheumatology is working to “find those dollars,” to alleviate the problems, he said, encouraging those who are concerned about the workforce issues to consider investing in the Rheumatology Research Foundation, which is a “huge supporter of rheumatology fellowships.”
Another proposal involves loan repayment plans for health professionals who agree to work at least 2 years in pediatric medicine.
“There’s an active bill that you can send an e-mail on right now,” Dr. Worthing said.
The bill, titled the “Educating Medical Professionals and Optimizing Workforce Efficiency and Readiness [EMPOWER] for Health Act,” represents an effort on the federal level to increase access to pediatric medical subspecialists by increasing the number who practice in underserved areas.
“It was introduced the day after we spoke on the Hill in May to leaders about this [issue],” he said.
Another effort is underway in Georgia, where a legislator who has lupus is working with the ACR on legislation that would allow the state to repay up to $25,000 on loans for cognitive specialists who agree to work in the state for a period of time.
The ACR is also working to maintain Deferred Action for Childhood Arrivals (DACA) protections for recipients pursuing medical education, who could potentially help to alleviate the shortages, he noted.
The problem of workforce issues is multifaceted and it requires a multipronged approach, Dr. Worthing said.
“It will not be solved by the American College of Rheumatology alone; I think it will end up being solved by people on the ground working with their primary care physicians and referring doctors to try to close the gap and try to see patients when they’re needed,” he said.
Dr. Worthing reported having no disclosures.
REPORTING FROM FSR 2019
Immune-related toxicities, hospitalization common with checkpoint inhibitor therapy
, according to a retrospective cohort study.
In addition, the majority of the immune-related toxicities were high-grade events of grade 3 or higher (65%), necessitated multidisciplinary care (91%), and eventually improved or resolved (65%). The results highlight potential risk factors for hospitalizations due to immune-related toxicities in oncology patients.
“[We aimed to] characterize the spectrum of toxicities, management, and outcomes of hospitalizations for immune-related adverse events,” wrote Aanika Balaji, BS, of Johns Hopkins University, Baltimore, and colleagues. The findings were reported in the Journal of Oncology Practice.
The researchers studied 443 patients admitted to solid tumor oncology service at an oncology center over a period of 6-months. Of these, 100 patients had at any point received checkpoint inhibitor therapy.
The proportion of hospital admissions for patients with confirmed immune-related toxicities and associations between hospitalizations due to immune-related toxicity and patient characteristics were assessed by the team. Nearly half of the patients admitted with immune-related toxicities had thoracic or head and neck cancers.
In the analysis, patients treated with combination checkpoint inhibitor therapy (odds ratio, 6.8; 95% confidence interval, 2.0-23.2), in addition to those aged 65 years and over (OR, 5.4; 95% CI, 1.6-17.8), were more likely to be hospitalized for immune-related toxicities.
Overall, 5% of all hospitalizations were the result of immune-related toxicities. Furthermore, 87% of patients discontinued checkpoint inhibitor therapy post discharge.
“We found that the most common immune-related adverse events warranting hospital admission were pneumonitis (26%) and colitis (17%),” they wrote.
The researchers acknowledged two key limitations of the study were the small sample size and lack of generalizability in community settings. Future studies that include patients from community oncology settings could improve the generalizability of the results.
“These data indicate potential risk factors for immune-related adverse event hospitalization and are likely to indicate future service needs” they concluded.
Financial support was provided by Jarushka Naidoo. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Compugen, Genentech, GlaxoSmithKline, Exelixis, MedImmune, and several others.
SOURCE: Balaji A et al. J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703.
, according to a retrospective cohort study.
In addition, the majority of the immune-related toxicities were high-grade events of grade 3 or higher (65%), necessitated multidisciplinary care (91%), and eventually improved or resolved (65%). The results highlight potential risk factors for hospitalizations due to immune-related toxicities in oncology patients.
“[We aimed to] characterize the spectrum of toxicities, management, and outcomes of hospitalizations for immune-related adverse events,” wrote Aanika Balaji, BS, of Johns Hopkins University, Baltimore, and colleagues. The findings were reported in the Journal of Oncology Practice.
The researchers studied 443 patients admitted to solid tumor oncology service at an oncology center over a period of 6-months. Of these, 100 patients had at any point received checkpoint inhibitor therapy.
The proportion of hospital admissions for patients with confirmed immune-related toxicities and associations between hospitalizations due to immune-related toxicity and patient characteristics were assessed by the team. Nearly half of the patients admitted with immune-related toxicities had thoracic or head and neck cancers.
In the analysis, patients treated with combination checkpoint inhibitor therapy (odds ratio, 6.8; 95% confidence interval, 2.0-23.2), in addition to those aged 65 years and over (OR, 5.4; 95% CI, 1.6-17.8), were more likely to be hospitalized for immune-related toxicities.
Overall, 5% of all hospitalizations were the result of immune-related toxicities. Furthermore, 87% of patients discontinued checkpoint inhibitor therapy post discharge.
“We found that the most common immune-related adverse events warranting hospital admission were pneumonitis (26%) and colitis (17%),” they wrote.
The researchers acknowledged two key limitations of the study were the small sample size and lack of generalizability in community settings. Future studies that include patients from community oncology settings could improve the generalizability of the results.
“These data indicate potential risk factors for immune-related adverse event hospitalization and are likely to indicate future service needs” they concluded.
Financial support was provided by Jarushka Naidoo. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Compugen, Genentech, GlaxoSmithKline, Exelixis, MedImmune, and several others.
SOURCE: Balaji A et al. J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703.
, according to a retrospective cohort study.
In addition, the majority of the immune-related toxicities were high-grade events of grade 3 or higher (65%), necessitated multidisciplinary care (91%), and eventually improved or resolved (65%). The results highlight potential risk factors for hospitalizations due to immune-related toxicities in oncology patients.
“[We aimed to] characterize the spectrum of toxicities, management, and outcomes of hospitalizations for immune-related adverse events,” wrote Aanika Balaji, BS, of Johns Hopkins University, Baltimore, and colleagues. The findings were reported in the Journal of Oncology Practice.
The researchers studied 443 patients admitted to solid tumor oncology service at an oncology center over a period of 6-months. Of these, 100 patients had at any point received checkpoint inhibitor therapy.
The proportion of hospital admissions for patients with confirmed immune-related toxicities and associations between hospitalizations due to immune-related toxicity and patient characteristics were assessed by the team. Nearly half of the patients admitted with immune-related toxicities had thoracic or head and neck cancers.
In the analysis, patients treated with combination checkpoint inhibitor therapy (odds ratio, 6.8; 95% confidence interval, 2.0-23.2), in addition to those aged 65 years and over (OR, 5.4; 95% CI, 1.6-17.8), were more likely to be hospitalized for immune-related toxicities.
Overall, 5% of all hospitalizations were the result of immune-related toxicities. Furthermore, 87% of patients discontinued checkpoint inhibitor therapy post discharge.
“We found that the most common immune-related adverse events warranting hospital admission were pneumonitis (26%) and colitis (17%),” they wrote.
The researchers acknowledged two key limitations of the study were the small sample size and lack of generalizability in community settings. Future studies that include patients from community oncology settings could improve the generalizability of the results.
“These data indicate potential risk factors for immune-related adverse event hospitalization and are likely to indicate future service needs” they concluded.
Financial support was provided by Jarushka Naidoo. The authors reported financial affiliations with AstraZeneca, Bristol-Myers Squibb, Compugen, Genentech, GlaxoSmithKline, Exelixis, MedImmune, and several others.
SOURCE: Balaji A et al. J Oncol Pract. 2019 Aug 6. doi: 10.1200/JOP.18.00703.
FROM JOURNAL OF ONCOLOGY PRACTICE
Oral semaglutide monotherapy delivers HbA1c improvements in type 2 diabetes
Oral semaglutide monotherapy was superior to placebo for improving glycated hemoglobin (HbA1c) levels at all doses tested in adults with type 2 diabetes who had been previously insufficiently managed with diet and exercise, according to findings from a global, randomized trial.
The drug also showed dose-dependent weight loss, with a statistically significant effect on body weight, compared with placebo, at higher doses.
To date, the glucagon-like peptide–1 receptor agonist has been available as weekly subcutaneous shots for patients with type 2 diabetes, and in that form they have been shown to be effective in reducing HbA1c, inducing weight loss, and lowering the risk of cardiovascular events in patients with cardiovascular disease or those who are at high risk for it, wrote Vanita R. Aroda, MD, of Brigham and Women’s Hospital, Boston, and colleagues. The report is in Diabetes Care.
The novel oral semaglutide tablet is designed to enhance medication absorption, and the pharmacokinetics and dosage were established in phase 2 studies, they noted.
In the phase 3 Peptide Innovation for Early Diabetes Treatment 1 (PIONEER 1) study, Dr. Aroda and colleagues randomized 703 adults with type 2 diabetes to receive either 3 mg, 7 mg, or 14 mg of oral semaglutide daily, or placebo. The average age of the patients was 55 years, about half were women, and the average baseline HbA1c was 8.0% (64 mmol/mol). The primary endpoint was change in HbA1c level from baseline to week 26, and the secondary endpoint was change in body weight over the same period.
After 26 weeks of once-daily treatment, patients in semaglutide group showed significant reductions in HbA1c from baseline with all three doses: –0.6% (3 mg), –0.9% (7 mg), and –1.1% (14 mg), with P less than .001 for all, based on an intention-to-treat analysis. Similar results occurred using an on-treatment analysis, with differences of –0.7%, –1.2%, and –1.4%, respectively, for the three doses.
In addition, patients in all dose groups achieved the secondary endpoint of reduction in body weight, compared with placebo, from baseline to 26 weeks based on both types of analyses. “Significantly more patients achieved body weight loss of at least 5% with oral semaglutide at 7 mg and 14 mg, compared with placebo,” Dr. Aroda and colleagues wrote (intention-to-treat: –0.1 for 3 mg daily [P = .87], –0.9 for 7 mg [P = .09], –2.3 for 14 mg [P less than .001]; and on-treatment: –0.2 for 3 mg [P = .71], –1.0 for 7 mg [P = .01], –2.6 for 14 mg [P less than .001]).
The overall incidence of adverse events and serious adverse events was similar in the treatment and placebo groups, with the most frequent being nausea and diarrhea. No deaths occurred among patients on the medication.
The findings were limited by several factors, including a patient population that had a relatively short duration of diabetes (mean, 3.5 years) and that the oral semaglutide was used as first-line monotherapy, without first using metformin, the researchers noted. However, oral semaglutide “achieved clinically meaningful and superior glucose lowering,” compared with placebo, at all three doses, they wrote.
“Ongoing additional studies in the PIONEER program will further define the effect when used in combination with other glucose-lowering therapies and in other populations of interest, such as those with high cardiovascular risk or renal impairment,” they emphasized
Novo Nordisk funded the study. The lead author disclosed relationships with Novo Nordisk, and several coauthors disclosed relationships with or employment by the company.
SOURCE: Aroda VR et al. Diabetes Care. 2019 Jul. doi: 10.2337/dc19-0749.
Oral semaglutide monotherapy was superior to placebo for improving glycated hemoglobin (HbA1c) levels at all doses tested in adults with type 2 diabetes who had been previously insufficiently managed with diet and exercise, according to findings from a global, randomized trial.
The drug also showed dose-dependent weight loss, with a statistically significant effect on body weight, compared with placebo, at higher doses.
To date, the glucagon-like peptide–1 receptor agonist has been available as weekly subcutaneous shots for patients with type 2 diabetes, and in that form they have been shown to be effective in reducing HbA1c, inducing weight loss, and lowering the risk of cardiovascular events in patients with cardiovascular disease or those who are at high risk for it, wrote Vanita R. Aroda, MD, of Brigham and Women’s Hospital, Boston, and colleagues. The report is in Diabetes Care.
The novel oral semaglutide tablet is designed to enhance medication absorption, and the pharmacokinetics and dosage were established in phase 2 studies, they noted.
In the phase 3 Peptide Innovation for Early Diabetes Treatment 1 (PIONEER 1) study, Dr. Aroda and colleagues randomized 703 adults with type 2 diabetes to receive either 3 mg, 7 mg, or 14 mg of oral semaglutide daily, or placebo. The average age of the patients was 55 years, about half were women, and the average baseline HbA1c was 8.0% (64 mmol/mol). The primary endpoint was change in HbA1c level from baseline to week 26, and the secondary endpoint was change in body weight over the same period.
After 26 weeks of once-daily treatment, patients in semaglutide group showed significant reductions in HbA1c from baseline with all three doses: –0.6% (3 mg), –0.9% (7 mg), and –1.1% (14 mg), with P less than .001 for all, based on an intention-to-treat analysis. Similar results occurred using an on-treatment analysis, with differences of –0.7%, –1.2%, and –1.4%, respectively, for the three doses.
In addition, patients in all dose groups achieved the secondary endpoint of reduction in body weight, compared with placebo, from baseline to 26 weeks based on both types of analyses. “Significantly more patients achieved body weight loss of at least 5% with oral semaglutide at 7 mg and 14 mg, compared with placebo,” Dr. Aroda and colleagues wrote (intention-to-treat: –0.1 for 3 mg daily [P = .87], –0.9 for 7 mg [P = .09], –2.3 for 14 mg [P less than .001]; and on-treatment: –0.2 for 3 mg [P = .71], –1.0 for 7 mg [P = .01], –2.6 for 14 mg [P less than .001]).
The overall incidence of adverse events and serious adverse events was similar in the treatment and placebo groups, with the most frequent being nausea and diarrhea. No deaths occurred among patients on the medication.
The findings were limited by several factors, including a patient population that had a relatively short duration of diabetes (mean, 3.5 years) and that the oral semaglutide was used as first-line monotherapy, without first using metformin, the researchers noted. However, oral semaglutide “achieved clinically meaningful and superior glucose lowering,” compared with placebo, at all three doses, they wrote.
“Ongoing additional studies in the PIONEER program will further define the effect when used in combination with other glucose-lowering therapies and in other populations of interest, such as those with high cardiovascular risk or renal impairment,” they emphasized
Novo Nordisk funded the study. The lead author disclosed relationships with Novo Nordisk, and several coauthors disclosed relationships with or employment by the company.
SOURCE: Aroda VR et al. Diabetes Care. 2019 Jul. doi: 10.2337/dc19-0749.
Oral semaglutide monotherapy was superior to placebo for improving glycated hemoglobin (HbA1c) levels at all doses tested in adults with type 2 diabetes who had been previously insufficiently managed with diet and exercise, according to findings from a global, randomized trial.
The drug also showed dose-dependent weight loss, with a statistically significant effect on body weight, compared with placebo, at higher doses.
To date, the glucagon-like peptide–1 receptor agonist has been available as weekly subcutaneous shots for patients with type 2 diabetes, and in that form they have been shown to be effective in reducing HbA1c, inducing weight loss, and lowering the risk of cardiovascular events in patients with cardiovascular disease or those who are at high risk for it, wrote Vanita R. Aroda, MD, of Brigham and Women’s Hospital, Boston, and colleagues. The report is in Diabetes Care.
The novel oral semaglutide tablet is designed to enhance medication absorption, and the pharmacokinetics and dosage were established in phase 2 studies, they noted.
In the phase 3 Peptide Innovation for Early Diabetes Treatment 1 (PIONEER 1) study, Dr. Aroda and colleagues randomized 703 adults with type 2 diabetes to receive either 3 mg, 7 mg, or 14 mg of oral semaglutide daily, or placebo. The average age of the patients was 55 years, about half were women, and the average baseline HbA1c was 8.0% (64 mmol/mol). The primary endpoint was change in HbA1c level from baseline to week 26, and the secondary endpoint was change in body weight over the same period.
After 26 weeks of once-daily treatment, patients in semaglutide group showed significant reductions in HbA1c from baseline with all three doses: –0.6% (3 mg), –0.9% (7 mg), and –1.1% (14 mg), with P less than .001 for all, based on an intention-to-treat analysis. Similar results occurred using an on-treatment analysis, with differences of –0.7%, –1.2%, and –1.4%, respectively, for the three doses.
In addition, patients in all dose groups achieved the secondary endpoint of reduction in body weight, compared with placebo, from baseline to 26 weeks based on both types of analyses. “Significantly more patients achieved body weight loss of at least 5% with oral semaglutide at 7 mg and 14 mg, compared with placebo,” Dr. Aroda and colleagues wrote (intention-to-treat: –0.1 for 3 mg daily [P = .87], –0.9 for 7 mg [P = .09], –2.3 for 14 mg [P less than .001]; and on-treatment: –0.2 for 3 mg [P = .71], –1.0 for 7 mg [P = .01], –2.6 for 14 mg [P less than .001]).
The overall incidence of adverse events and serious adverse events was similar in the treatment and placebo groups, with the most frequent being nausea and diarrhea. No deaths occurred among patients on the medication.
The findings were limited by several factors, including a patient population that had a relatively short duration of diabetes (mean, 3.5 years) and that the oral semaglutide was used as first-line monotherapy, without first using metformin, the researchers noted. However, oral semaglutide “achieved clinically meaningful and superior glucose lowering,” compared with placebo, at all three doses, they wrote.
“Ongoing additional studies in the PIONEER program will further define the effect when used in combination with other glucose-lowering therapies and in other populations of interest, such as those with high cardiovascular risk or renal impairment,” they emphasized
Novo Nordisk funded the study. The lead author disclosed relationships with Novo Nordisk, and several coauthors disclosed relationships with or employment by the company.
SOURCE: Aroda VR et al. Diabetes Care. 2019 Jul. doi: 10.2337/dc19-0749.
FROM DIABETES CARE