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Low-income uninsured trauma patients at risk for ruinous medical costs
Almost three-quarters of uninsured adults admitted for traumatic injury are at risk of catastrophic health expenditures (CHEs), according to a large retrospective study from a national patient database.
Since enactment of the Affordable Care Act in 2010, the number of uninsured individuals has dropped substantially, but there remains a large population of younger adults, many from low-income areas, who still are not covered. The Centers for Disease Control and Prevention reported in 2015 that 12.8% of individuals aged 18-64 years were uninsured. The financial impact of a traumatic injury is likely to be significant for those paying out of pocket, but the question of who is at risk and to what degree is understudied, according to John W. Scott, MD, of Brigham and Women’s Hospital, Boston, and his colleagues.
“Defining populations at risk of financial catastrophe after medical expense is a necessary step towards elucidating the effect of health care reforms intended to increase access to healthcare through insurance expansion,” they wrote in the Annals of Surgery (2017 Apr 7. doi: 10.1097/SLA.0000000000002254).
Dr. Scott and his colleagues analyzed trauma diagnoses in adults aged 18-64 years from Nationwide Inpatient Sample 2007-2011. They used the U.S. Census data to estimate post-subsistence income (income remaining after paying for food) and hospital charges for trauma diagnoses. The sample of 117,502 patient encounters was weighted to represent 579,683 trauma patients in the national database.
CHEs were defined conservatively as expenses that exceed 40% of a patient’s post-subsistence income; they also applied a lower threshold of CHEs – 10% of a patient’s entire income – without accounting for subsistence needs.
The investigators wanted to look at who was at greatest risk for CHEs and used the Census data to sort trauma patients by residential zip code to identify the distribution of income in the sample.
Costs to trauma patients varied by injury severity score (ISS) and by income quartile. Patients in the 25th income quartile paid less for their treatment, even accounting for ISS, but despite this difference, poorer patients were at a much greater risk for CHEs.
The median charge for all of these uninsured trauma patients was $27,420. Those trauma patients in the 25th percentile of income were charged an average of $15,196, while those in 75th quartile were charged $49,696. The difference in costs also was evident when comparing patients in different ISS categories: for ISS 9-15, median trauma costs for the lower-quartile patients was $31,095, but costs for the upper quartile patients was $52,639.
With cost, income, and injury severity data, the investigators found that overall the proportion of adults aged 18-64 years at risk for CHEs was 70.8% (95% confidence interval, 70.7%-71.1%). Subpopulations (ethnicity/race, age, sex) were within a few percentage point of each other.
Risk of CHEs varied widely by income quartile and ISS. Uninsured trauma patients in the highest income quartile had a 52.9% risk of CHEs, compared with 77.5% of those in the lowest-income quartile. Overall, 81.8% of patients with ISS greater than 24 were at risk for CHEs. In addition, the study found that patients treated at large or urban teaching hospitals – those most likely to handle the most-severely injured patients – were at a heightened risk for CHEs.
When the investigators conducted the same analysis with a lower threshold of CHEs (10% of income, not including subsistence expenses), the overall risk for uninsured trauma patients for catastrophic health expenses was more than 90%.
“Trauma patients are at particularly high risk for CHE because trauma disproportionately affects uninsured patients with little disposable income and because trauma injuries commonly affect multiple organ systems and incur expensive, multispecialty care,” Dr. Scott and his colleagues wrote. “Large unpaid medical debts may have longstanding impacts on patients’ financial well-being, affecting credit ratings and overall financial solvency. These financial stresses may be further compounded by an inability to return to work caused by injury.”
Dr. Scott and his coauthors added that having health insurance does not entirely eliminate the risk for CHEs and that individuals in the lower income brackets covered by employer-based plans or Medicaid had difficulty paying medical bills.
Only hospital costs were examined, which may not reflect forgiven debts, the investigators noted. In addition, the costs may be underreported because they do not include physician charges, postacute care, home health care, or rehabilitation. Incomes were estimated by zip code analysis, which may misclassify some individuals.
“Efforts are needed to ensure that the lifesaving care provided by our highly coordinated trauma systems do not have the unintended consequence of curing patients into destitution,” Dr. Scott and his colleagues wrote
The authors declared no conflicts of interest.
Almost three-quarters of uninsured adults admitted for traumatic injury are at risk of catastrophic health expenditures (CHEs), according to a large retrospective study from a national patient database.
Since enactment of the Affordable Care Act in 2010, the number of uninsured individuals has dropped substantially, but there remains a large population of younger adults, many from low-income areas, who still are not covered. The Centers for Disease Control and Prevention reported in 2015 that 12.8% of individuals aged 18-64 years were uninsured. The financial impact of a traumatic injury is likely to be significant for those paying out of pocket, but the question of who is at risk and to what degree is understudied, according to John W. Scott, MD, of Brigham and Women’s Hospital, Boston, and his colleagues.
“Defining populations at risk of financial catastrophe after medical expense is a necessary step towards elucidating the effect of health care reforms intended to increase access to healthcare through insurance expansion,” they wrote in the Annals of Surgery (2017 Apr 7. doi: 10.1097/SLA.0000000000002254).
Dr. Scott and his colleagues analyzed trauma diagnoses in adults aged 18-64 years from Nationwide Inpatient Sample 2007-2011. They used the U.S. Census data to estimate post-subsistence income (income remaining after paying for food) and hospital charges for trauma diagnoses. The sample of 117,502 patient encounters was weighted to represent 579,683 trauma patients in the national database.
CHEs were defined conservatively as expenses that exceed 40% of a patient’s post-subsistence income; they also applied a lower threshold of CHEs – 10% of a patient’s entire income – without accounting for subsistence needs.
The investigators wanted to look at who was at greatest risk for CHEs and used the Census data to sort trauma patients by residential zip code to identify the distribution of income in the sample.
Costs to trauma patients varied by injury severity score (ISS) and by income quartile. Patients in the 25th income quartile paid less for their treatment, even accounting for ISS, but despite this difference, poorer patients were at a much greater risk for CHEs.
The median charge for all of these uninsured trauma patients was $27,420. Those trauma patients in the 25th percentile of income were charged an average of $15,196, while those in 75th quartile were charged $49,696. The difference in costs also was evident when comparing patients in different ISS categories: for ISS 9-15, median trauma costs for the lower-quartile patients was $31,095, but costs for the upper quartile patients was $52,639.
With cost, income, and injury severity data, the investigators found that overall the proportion of adults aged 18-64 years at risk for CHEs was 70.8% (95% confidence interval, 70.7%-71.1%). Subpopulations (ethnicity/race, age, sex) were within a few percentage point of each other.
Risk of CHEs varied widely by income quartile and ISS. Uninsured trauma patients in the highest income quartile had a 52.9% risk of CHEs, compared with 77.5% of those in the lowest-income quartile. Overall, 81.8% of patients with ISS greater than 24 were at risk for CHEs. In addition, the study found that patients treated at large or urban teaching hospitals – those most likely to handle the most-severely injured patients – were at a heightened risk for CHEs.
When the investigators conducted the same analysis with a lower threshold of CHEs (10% of income, not including subsistence expenses), the overall risk for uninsured trauma patients for catastrophic health expenses was more than 90%.
“Trauma patients are at particularly high risk for CHE because trauma disproportionately affects uninsured patients with little disposable income and because trauma injuries commonly affect multiple organ systems and incur expensive, multispecialty care,” Dr. Scott and his colleagues wrote. “Large unpaid medical debts may have longstanding impacts on patients’ financial well-being, affecting credit ratings and overall financial solvency. These financial stresses may be further compounded by an inability to return to work caused by injury.”
Dr. Scott and his coauthors added that having health insurance does not entirely eliminate the risk for CHEs and that individuals in the lower income brackets covered by employer-based plans or Medicaid had difficulty paying medical bills.
Only hospital costs were examined, which may not reflect forgiven debts, the investigators noted. In addition, the costs may be underreported because they do not include physician charges, postacute care, home health care, or rehabilitation. Incomes were estimated by zip code analysis, which may misclassify some individuals.
“Efforts are needed to ensure that the lifesaving care provided by our highly coordinated trauma systems do not have the unintended consequence of curing patients into destitution,” Dr. Scott and his colleagues wrote
The authors declared no conflicts of interest.
Almost three-quarters of uninsured adults admitted for traumatic injury are at risk of catastrophic health expenditures (CHEs), according to a large retrospective study from a national patient database.
Since enactment of the Affordable Care Act in 2010, the number of uninsured individuals has dropped substantially, but there remains a large population of younger adults, many from low-income areas, who still are not covered. The Centers for Disease Control and Prevention reported in 2015 that 12.8% of individuals aged 18-64 years were uninsured. The financial impact of a traumatic injury is likely to be significant for those paying out of pocket, but the question of who is at risk and to what degree is understudied, according to John W. Scott, MD, of Brigham and Women’s Hospital, Boston, and his colleagues.
“Defining populations at risk of financial catastrophe after medical expense is a necessary step towards elucidating the effect of health care reforms intended to increase access to healthcare through insurance expansion,” they wrote in the Annals of Surgery (2017 Apr 7. doi: 10.1097/SLA.0000000000002254).
Dr. Scott and his colleagues analyzed trauma diagnoses in adults aged 18-64 years from Nationwide Inpatient Sample 2007-2011. They used the U.S. Census data to estimate post-subsistence income (income remaining after paying for food) and hospital charges for trauma diagnoses. The sample of 117,502 patient encounters was weighted to represent 579,683 trauma patients in the national database.
CHEs were defined conservatively as expenses that exceed 40% of a patient’s post-subsistence income; they also applied a lower threshold of CHEs – 10% of a patient’s entire income – without accounting for subsistence needs.
The investigators wanted to look at who was at greatest risk for CHEs and used the Census data to sort trauma patients by residential zip code to identify the distribution of income in the sample.
Costs to trauma patients varied by injury severity score (ISS) and by income quartile. Patients in the 25th income quartile paid less for their treatment, even accounting for ISS, but despite this difference, poorer patients were at a much greater risk for CHEs.
The median charge for all of these uninsured trauma patients was $27,420. Those trauma patients in the 25th percentile of income were charged an average of $15,196, while those in 75th quartile were charged $49,696. The difference in costs also was evident when comparing patients in different ISS categories: for ISS 9-15, median trauma costs for the lower-quartile patients was $31,095, but costs for the upper quartile patients was $52,639.
With cost, income, and injury severity data, the investigators found that overall the proportion of adults aged 18-64 years at risk for CHEs was 70.8% (95% confidence interval, 70.7%-71.1%). Subpopulations (ethnicity/race, age, sex) were within a few percentage point of each other.
Risk of CHEs varied widely by income quartile and ISS. Uninsured trauma patients in the highest income quartile had a 52.9% risk of CHEs, compared with 77.5% of those in the lowest-income quartile. Overall, 81.8% of patients with ISS greater than 24 were at risk for CHEs. In addition, the study found that patients treated at large or urban teaching hospitals – those most likely to handle the most-severely injured patients – were at a heightened risk for CHEs.
When the investigators conducted the same analysis with a lower threshold of CHEs (10% of income, not including subsistence expenses), the overall risk for uninsured trauma patients for catastrophic health expenses was more than 90%.
“Trauma patients are at particularly high risk for CHE because trauma disproportionately affects uninsured patients with little disposable income and because trauma injuries commonly affect multiple organ systems and incur expensive, multispecialty care,” Dr. Scott and his colleagues wrote. “Large unpaid medical debts may have longstanding impacts on patients’ financial well-being, affecting credit ratings and overall financial solvency. These financial stresses may be further compounded by an inability to return to work caused by injury.”
Dr. Scott and his coauthors added that having health insurance does not entirely eliminate the risk for CHEs and that individuals in the lower income brackets covered by employer-based plans or Medicaid had difficulty paying medical bills.
Only hospital costs were examined, which may not reflect forgiven debts, the investigators noted. In addition, the costs may be underreported because they do not include physician charges, postacute care, home health care, or rehabilitation. Incomes were estimated by zip code analysis, which may misclassify some individuals.
“Efforts are needed to ensure that the lifesaving care provided by our highly coordinated trauma systems do not have the unintended consequence of curing patients into destitution,” Dr. Scott and his colleagues wrote
The authors declared no conflicts of interest.
FROM ANNALS OF SURGERY
Postop pain may be a predictor for readmission
PHILADELPHIA – How a patient reacts to postoperative pain and how the pain progresses or regresses can be key predictors for 30-day hospital readmissions and emergency department visits after hospital discharge, according to an analysis of more than 200,000 operations in a national database.
The study sample included 211,213 operations in the Veterans Affairs Surgical Quality Improvement Program during 2008-2014, 45% of which were orthopedic in nature, 37% general, and 18% vascular. The overall 30-day unplanned readmission rate was 10.8% and the 30-day ED utilization rate was 14.2%, Dr. Hawn said.
The study identified six distinct postoperative inpatient pain trajectories based on postop pain scores: persistently low (4.5%); mild to low (9%); persistently mild (15.3%); moderate to low (12.1%); persistently moderate (40.2%); and persistently high (18.9%). One of the study objectives, Dr. Hawn said, “was to see if we could identify patterns of postoperative pain trajectories in a surgical cohort, and to describe these subpopulations by their trajectories, and then to determine whether there was an association with postdischarge health care utilization.” The hypothesis was that inpatient postoperative pain trajectory would be associated with 30-day readmission and ED visits as well as postop complications, Dr. Hawn added.
Patients with high pain trajectories had highest rates of postdischarge readmission and ED visits, 14.4% and 16.3%, respectively, Dr. Hawn said.
“Patients in the low-pain categories were more likely to undergo general and vascular procedures compared to orthopedic procedures in the high-pain categories,” Dr. Hawn said. “In the low-pain categories, they were older and less likely to be female. They were less likely to have independent functional status whereas patients in the high-pain category had a 26% prevalence of preoperative diagnosis of depression.”
Those in the high-pain category had a 1.5 times greater risk of an unplanned readmission and a 4 times greater risk in pain-related readmission, according to an odds ratio analysis of the data.
“As for the prevalence of our outcomes, 10.7% had an unplanned readmission. A total of 1.5% from the overall cohort had a pain-related readmission, 8.6% had an emergency visit within 30 days of discharge that did not result in a readmission, and 4.4% had at least one postdischarge complication,” Dr. Hawn said.
In his discussion, Clifford Y. Ko, MD, FACS, of the University of California, Los Angeles, asked what was the take-home for surgeons managing patients postoperatively in the era of the opioid epidemic. “For these types of patients, we need to get our colleagues, the pain specialists, involved much earlier,” Dr. Hawn said. “We need to rethink that strategy of treating the pain-score number. And I think there’s been so much national attention to this that we will stop focusing on that number as a measure of quality of care and patient satisfaction. Those are some trends we’ll see in the future.”
Neither Dr. Hawn nor Dr. Ko reported any financial disclosures
The complete manuscript of this study and its presentation at the American Surgical Association’s 137th Annual Meeting, April 2017, in Philadelphia, is anticipated to be published in the Annals of Surgery pending editorial review.
PHILADELPHIA – How a patient reacts to postoperative pain and how the pain progresses or regresses can be key predictors for 30-day hospital readmissions and emergency department visits after hospital discharge, according to an analysis of more than 200,000 operations in a national database.
The study sample included 211,213 operations in the Veterans Affairs Surgical Quality Improvement Program during 2008-2014, 45% of which were orthopedic in nature, 37% general, and 18% vascular. The overall 30-day unplanned readmission rate was 10.8% and the 30-day ED utilization rate was 14.2%, Dr. Hawn said.
The study identified six distinct postoperative inpatient pain trajectories based on postop pain scores: persistently low (4.5%); mild to low (9%); persistently mild (15.3%); moderate to low (12.1%); persistently moderate (40.2%); and persistently high (18.9%). One of the study objectives, Dr. Hawn said, “was to see if we could identify patterns of postoperative pain trajectories in a surgical cohort, and to describe these subpopulations by their trajectories, and then to determine whether there was an association with postdischarge health care utilization.” The hypothesis was that inpatient postoperative pain trajectory would be associated with 30-day readmission and ED visits as well as postop complications, Dr. Hawn added.
Patients with high pain trajectories had highest rates of postdischarge readmission and ED visits, 14.4% and 16.3%, respectively, Dr. Hawn said.
“Patients in the low-pain categories were more likely to undergo general and vascular procedures compared to orthopedic procedures in the high-pain categories,” Dr. Hawn said. “In the low-pain categories, they were older and less likely to be female. They were less likely to have independent functional status whereas patients in the high-pain category had a 26% prevalence of preoperative diagnosis of depression.”
Those in the high-pain category had a 1.5 times greater risk of an unplanned readmission and a 4 times greater risk in pain-related readmission, according to an odds ratio analysis of the data.
“As for the prevalence of our outcomes, 10.7% had an unplanned readmission. A total of 1.5% from the overall cohort had a pain-related readmission, 8.6% had an emergency visit within 30 days of discharge that did not result in a readmission, and 4.4% had at least one postdischarge complication,” Dr. Hawn said.
In his discussion, Clifford Y. Ko, MD, FACS, of the University of California, Los Angeles, asked what was the take-home for surgeons managing patients postoperatively in the era of the opioid epidemic. “For these types of patients, we need to get our colleagues, the pain specialists, involved much earlier,” Dr. Hawn said. “We need to rethink that strategy of treating the pain-score number. And I think there’s been so much national attention to this that we will stop focusing on that number as a measure of quality of care and patient satisfaction. Those are some trends we’ll see in the future.”
Neither Dr. Hawn nor Dr. Ko reported any financial disclosures
The complete manuscript of this study and its presentation at the American Surgical Association’s 137th Annual Meeting, April 2017, in Philadelphia, is anticipated to be published in the Annals of Surgery pending editorial review.
PHILADELPHIA – How a patient reacts to postoperative pain and how the pain progresses or regresses can be key predictors for 30-day hospital readmissions and emergency department visits after hospital discharge, according to an analysis of more than 200,000 operations in a national database.
The study sample included 211,213 operations in the Veterans Affairs Surgical Quality Improvement Program during 2008-2014, 45% of which were orthopedic in nature, 37% general, and 18% vascular. The overall 30-day unplanned readmission rate was 10.8% and the 30-day ED utilization rate was 14.2%, Dr. Hawn said.
The study identified six distinct postoperative inpatient pain trajectories based on postop pain scores: persistently low (4.5%); mild to low (9%); persistently mild (15.3%); moderate to low (12.1%); persistently moderate (40.2%); and persistently high (18.9%). One of the study objectives, Dr. Hawn said, “was to see if we could identify patterns of postoperative pain trajectories in a surgical cohort, and to describe these subpopulations by their trajectories, and then to determine whether there was an association with postdischarge health care utilization.” The hypothesis was that inpatient postoperative pain trajectory would be associated with 30-day readmission and ED visits as well as postop complications, Dr. Hawn added.
Patients with high pain trajectories had highest rates of postdischarge readmission and ED visits, 14.4% and 16.3%, respectively, Dr. Hawn said.
“Patients in the low-pain categories were more likely to undergo general and vascular procedures compared to orthopedic procedures in the high-pain categories,” Dr. Hawn said. “In the low-pain categories, they were older and less likely to be female. They were less likely to have independent functional status whereas patients in the high-pain category had a 26% prevalence of preoperative diagnosis of depression.”
Those in the high-pain category had a 1.5 times greater risk of an unplanned readmission and a 4 times greater risk in pain-related readmission, according to an odds ratio analysis of the data.
“As for the prevalence of our outcomes, 10.7% had an unplanned readmission. A total of 1.5% from the overall cohort had a pain-related readmission, 8.6% had an emergency visit within 30 days of discharge that did not result in a readmission, and 4.4% had at least one postdischarge complication,” Dr. Hawn said.
In his discussion, Clifford Y. Ko, MD, FACS, of the University of California, Los Angeles, asked what was the take-home for surgeons managing patients postoperatively in the era of the opioid epidemic. “For these types of patients, we need to get our colleagues, the pain specialists, involved much earlier,” Dr. Hawn said. “We need to rethink that strategy of treating the pain-score number. And I think there’s been so much national attention to this that we will stop focusing on that number as a measure of quality of care and patient satisfaction. Those are some trends we’ll see in the future.”
Neither Dr. Hawn nor Dr. Ko reported any financial disclosures
The complete manuscript of this study and its presentation at the American Surgical Association’s 137th Annual Meeting, April 2017, in Philadelphia, is anticipated to be published in the Annals of Surgery pending editorial review.
AT THE ASA ANNUAL
Key clinical point: A higher trajectory of postoperative pain scores may be a predictor of 30-day readmission and emergency department utilization.
Major finding: Patients with high pain trajectories had the highest rates of post-discharge readmission and emergency department visits, 14.4% and 16.3%, respectively.
Data source: Retrospective cohort study of Veterans Affairs’ data on operations on 211,213 operations performed during 2008-2014.
Disclosures: Dr. Hawn and her coauthors reported having no financial disclosures.
Lower limb compression halved epidural-associated hypotension
SAN DIEGO – Use of sequential compression devices reduced by half cases of epidural-associated hypotension in laboring women in a small real-world, randomized controlled trial.
The results showed that patients who received sequential compression devices (SCD) and kept them on for at least an hour after epidural analgesia placement had half the hypotension of patients who had no lower limb compression (33.3% vs. 66.7%; P .022).
“Lower limb compression using SCDs significantly decreased the incidence of maternal hypotension in laboring patients receiving epidural anesthesia,” said Margaret Steinmetz, MD, a third-year resident at the State University of New York at Buffalo.
The study, which was presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists, was a multisite, randomized controlled trial that used a randomized block design to assign women to three groups. The control group received no intervention; the remainder of patients received either thromboembolic deterrent (TED) stockings or sequential compression devices (SCDs) set to intermittent compression and applied before receiving epidural anesthesia.
The facilities’ usual protocols were followed both for epidural placement and for patient management, except for the lower limb compression and the study’s timed blood pressure checks.
Pregnant women who were at term and had requested epidural anesthesia were included if they had a singleton pregnancy; no history of hypertension, cardiovascular disease; and no contraindication to lower limb compression.
Hypotension – defined as at least one decrease in either systolic or diastolic blood pressure of more than 20% from baseline – was tracked by obtaining sequential blood pressure readings. A baseline was established with an average of three readings obtained before epidural placement. Following the epidural bolus, blood pressures were measured at minutes 1, 5, 15, 30, 45, and 60.
The investigators used an intention-to-treat analysis, meaning that they included patients allocated to each group whether or not they actually received lower limb compression. Patients with missing data were excluded.
A total of 82 patients were randomized:
- 28 to the control arm (no lower limb compression); 1 had missing data.
- 26 to receive TEDs (6 of whom did not don the stockings); 5 were excluded from analysis because of missing data or no epidural placement.
- 28 patients to receive SCDs (8 of whom did not have SCDs applied); 5 were excluded from analysis because of missing data or no epidural placement.
While the SCDs cut the incidence of hypotension in half, compared with no compression, women in the TEDs group saw an intermediate result, with a 52.4% incidence of hypotension.
Dr. Steinmetz noted that knee-high TEDs were used. The choice was made in part because the labor and delivery nursing staff were not enthusiastic about the prospect of placing thigh-high TEDs on a woman in labor, she added.
Patient age, mean body mass index, and gestational age did not differ significantly between the study arms. Logistic regression analysis performed to control for clinical site, method of delivery, gestational age, and maternal age and body mass index did not affect the analysis, Dr. Steinmetz added.
Older data showed that about 30% of women getting epidurals in labor experience hypotension, though Dr. Steinmetz said that she believes that the 66.7% seen in this study is probably closer to an accurate estimate.
SUNY Buffalo is looking at changing the labor and delivery protocol to include lower limb compression with epidurals, Dr. Steinmetz said, adding “When I’m on labor and delivery, I definitely encourage the placement of SCDs.”
Some facilities also use lower limb compression to reduce hypotension when patients receive regional anesthesia for cesarean deliveries. Dr. Steinmetz said that there are studies that support that practice, but the literature is not conclusive. Still, it makes sense in this setting too, she said. “C-section patients sit up, they get their spinal, then we lay them down and put in a Foley, and they’re vomiting as we put in the Foley because they’re hypotensive from that spinal. ... For me, myself, when I go into practice in 2 months, yes; I will be wanting to do this.”
Dr. Steinmetz reported no relevant disclosures.
[email protected]
On Twitter @karioakes
SAN DIEGO – Use of sequential compression devices reduced by half cases of epidural-associated hypotension in laboring women in a small real-world, randomized controlled trial.
The results showed that patients who received sequential compression devices (SCD) and kept them on for at least an hour after epidural analgesia placement had half the hypotension of patients who had no lower limb compression (33.3% vs. 66.7%; P .022).
“Lower limb compression using SCDs significantly decreased the incidence of maternal hypotension in laboring patients receiving epidural anesthesia,” said Margaret Steinmetz, MD, a third-year resident at the State University of New York at Buffalo.
The study, which was presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists, was a multisite, randomized controlled trial that used a randomized block design to assign women to three groups. The control group received no intervention; the remainder of patients received either thromboembolic deterrent (TED) stockings or sequential compression devices (SCDs) set to intermittent compression and applied before receiving epidural anesthesia.
The facilities’ usual protocols were followed both for epidural placement and for patient management, except for the lower limb compression and the study’s timed blood pressure checks.
Pregnant women who were at term and had requested epidural anesthesia were included if they had a singleton pregnancy; no history of hypertension, cardiovascular disease; and no contraindication to lower limb compression.
Hypotension – defined as at least one decrease in either systolic or diastolic blood pressure of more than 20% from baseline – was tracked by obtaining sequential blood pressure readings. A baseline was established with an average of three readings obtained before epidural placement. Following the epidural bolus, blood pressures were measured at minutes 1, 5, 15, 30, 45, and 60.
The investigators used an intention-to-treat analysis, meaning that they included patients allocated to each group whether or not they actually received lower limb compression. Patients with missing data were excluded.
A total of 82 patients were randomized:
- 28 to the control arm (no lower limb compression); 1 had missing data.
- 26 to receive TEDs (6 of whom did not don the stockings); 5 were excluded from analysis because of missing data or no epidural placement.
- 28 patients to receive SCDs (8 of whom did not have SCDs applied); 5 were excluded from analysis because of missing data or no epidural placement.
While the SCDs cut the incidence of hypotension in half, compared with no compression, women in the TEDs group saw an intermediate result, with a 52.4% incidence of hypotension.
Dr. Steinmetz noted that knee-high TEDs were used. The choice was made in part because the labor and delivery nursing staff were not enthusiastic about the prospect of placing thigh-high TEDs on a woman in labor, she added.
Patient age, mean body mass index, and gestational age did not differ significantly between the study arms. Logistic regression analysis performed to control for clinical site, method of delivery, gestational age, and maternal age and body mass index did not affect the analysis, Dr. Steinmetz added.
Older data showed that about 30% of women getting epidurals in labor experience hypotension, though Dr. Steinmetz said that she believes that the 66.7% seen in this study is probably closer to an accurate estimate.
SUNY Buffalo is looking at changing the labor and delivery protocol to include lower limb compression with epidurals, Dr. Steinmetz said, adding “When I’m on labor and delivery, I definitely encourage the placement of SCDs.”
Some facilities also use lower limb compression to reduce hypotension when patients receive regional anesthesia for cesarean deliveries. Dr. Steinmetz said that there are studies that support that practice, but the literature is not conclusive. Still, it makes sense in this setting too, she said. “C-section patients sit up, they get their spinal, then we lay them down and put in a Foley, and they’re vomiting as we put in the Foley because they’re hypotensive from that spinal. ... For me, myself, when I go into practice in 2 months, yes; I will be wanting to do this.”
Dr. Steinmetz reported no relevant disclosures.
[email protected]
On Twitter @karioakes
SAN DIEGO – Use of sequential compression devices reduced by half cases of epidural-associated hypotension in laboring women in a small real-world, randomized controlled trial.
The results showed that patients who received sequential compression devices (SCD) and kept them on for at least an hour after epidural analgesia placement had half the hypotension of patients who had no lower limb compression (33.3% vs. 66.7%; P .022).
“Lower limb compression using SCDs significantly decreased the incidence of maternal hypotension in laboring patients receiving epidural anesthesia,” said Margaret Steinmetz, MD, a third-year resident at the State University of New York at Buffalo.
The study, which was presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists, was a multisite, randomized controlled trial that used a randomized block design to assign women to three groups. The control group received no intervention; the remainder of patients received either thromboembolic deterrent (TED) stockings or sequential compression devices (SCDs) set to intermittent compression and applied before receiving epidural anesthesia.
The facilities’ usual protocols were followed both for epidural placement and for patient management, except for the lower limb compression and the study’s timed blood pressure checks.
Pregnant women who were at term and had requested epidural anesthesia were included if they had a singleton pregnancy; no history of hypertension, cardiovascular disease; and no contraindication to lower limb compression.
Hypotension – defined as at least one decrease in either systolic or diastolic blood pressure of more than 20% from baseline – was tracked by obtaining sequential blood pressure readings. A baseline was established with an average of three readings obtained before epidural placement. Following the epidural bolus, blood pressures were measured at minutes 1, 5, 15, 30, 45, and 60.
The investigators used an intention-to-treat analysis, meaning that they included patients allocated to each group whether or not they actually received lower limb compression. Patients with missing data were excluded.
A total of 82 patients were randomized:
- 28 to the control arm (no lower limb compression); 1 had missing data.
- 26 to receive TEDs (6 of whom did not don the stockings); 5 were excluded from analysis because of missing data or no epidural placement.
- 28 patients to receive SCDs (8 of whom did not have SCDs applied); 5 were excluded from analysis because of missing data or no epidural placement.
While the SCDs cut the incidence of hypotension in half, compared with no compression, women in the TEDs group saw an intermediate result, with a 52.4% incidence of hypotension.
Dr. Steinmetz noted that knee-high TEDs were used. The choice was made in part because the labor and delivery nursing staff were not enthusiastic about the prospect of placing thigh-high TEDs on a woman in labor, she added.
Patient age, mean body mass index, and gestational age did not differ significantly between the study arms. Logistic regression analysis performed to control for clinical site, method of delivery, gestational age, and maternal age and body mass index did not affect the analysis, Dr. Steinmetz added.
Older data showed that about 30% of women getting epidurals in labor experience hypotension, though Dr. Steinmetz said that she believes that the 66.7% seen in this study is probably closer to an accurate estimate.
SUNY Buffalo is looking at changing the labor and delivery protocol to include lower limb compression with epidurals, Dr. Steinmetz said, adding “When I’m on labor and delivery, I definitely encourage the placement of SCDs.”
Some facilities also use lower limb compression to reduce hypotension when patients receive regional anesthesia for cesarean deliveries. Dr. Steinmetz said that there are studies that support that practice, but the literature is not conclusive. Still, it makes sense in this setting too, she said. “C-section patients sit up, they get their spinal, then we lay them down and put in a Foley, and they’re vomiting as we put in the Foley because they’re hypotensive from that spinal. ... For me, myself, when I go into practice in 2 months, yes; I will be wanting to do this.”
Dr. Steinmetz reported no relevant disclosures.
[email protected]
On Twitter @karioakes
AT ACOG 2017
Key clinical point:
Major finding: The rate of hypotension for women in labor who received epidurals was 66.7% with no lower limb compression, compared with 33.3% when sequential compression devices were used (P –.02).
Data source: Multisite randomized controlled trial of 82 patients who received epidurals while in labor.
Disclosures: The study authors reported no outside sources of funding, and reported no conflicts of interest.
Enzyme tablet eases pain of gluten consumption
CHICAGO – Gluten-sensitive patients were able to tolerate small amounts of gluten after consuming an enzyme supplement derived from Aspergillus niger as part of a meal in a randomized, placebo-controlled trial of 18 adults. The data were presented at the annual Digestive Disease Week.
The enzyme, A. niger-derived prolyl endoprotease (AN-PEP), has demonstrated the ability to degrade gluten into nonimmunogenic compounds in vivo in healthy subjects, according to Julia König, PhD, of the School of Medical Sciences, Örebro (Sweden) University and her colleagues. The researchers tested the enzyme at two separate doses in 18 adults with self-reported gluten sensitivity.
The participants’ gastric and duodenal content was sampled several times over 180 minutes and analyzed for gluten epitopes using an enzyme-linked immunosorbent assay test. Participants also completed questionnaires after each day of testing.
After taking the enzyme in conjunction with the gluten, stomach gluten content averaged 31 microg x min/mL in the high-dose and low-dose enzyme patients (P = 0.001 for both doses), compared with 281 microg x min/mL in the placebo patients.
By the time the gluten reached the duodenum, the average levels had dropped to 12 microg x min/mL in the high-dose patients (P = 0.019) and 8 microg x min/mL in the low-dose patients (P = 0.015), compared with an average of 65 microg x min/mL in the placebo patients.
Overall, the enzyme was well tolerated by the patients, the researchers said. However, Dr. König emphasized that the enzyme tablet is meant to help avoid symptoms when gluten-sensitive patients encounter small amounts of gluten, and these patients should still follow a gluten-free diet.
AN-PEP is available in the United States in supplement form under several names and is manufactured by the Dutch company DSM. The AN-PEP enzyme used in the study was provided by DSM, but the company provided no other support. Dr. König had no relevant financial conflicts to disclose.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – Gluten-sensitive patients were able to tolerate small amounts of gluten after consuming an enzyme supplement derived from Aspergillus niger as part of a meal in a randomized, placebo-controlled trial of 18 adults. The data were presented at the annual Digestive Disease Week.
The enzyme, A. niger-derived prolyl endoprotease (AN-PEP), has demonstrated the ability to degrade gluten into nonimmunogenic compounds in vivo in healthy subjects, according to Julia König, PhD, of the School of Medical Sciences, Örebro (Sweden) University and her colleagues. The researchers tested the enzyme at two separate doses in 18 adults with self-reported gluten sensitivity.
The participants’ gastric and duodenal content was sampled several times over 180 minutes and analyzed for gluten epitopes using an enzyme-linked immunosorbent assay test. Participants also completed questionnaires after each day of testing.
After taking the enzyme in conjunction with the gluten, stomach gluten content averaged 31 microg x min/mL in the high-dose and low-dose enzyme patients (P = 0.001 for both doses), compared with 281 microg x min/mL in the placebo patients.
By the time the gluten reached the duodenum, the average levels had dropped to 12 microg x min/mL in the high-dose patients (P = 0.019) and 8 microg x min/mL in the low-dose patients (P = 0.015), compared with an average of 65 microg x min/mL in the placebo patients.
Overall, the enzyme was well tolerated by the patients, the researchers said. However, Dr. König emphasized that the enzyme tablet is meant to help avoid symptoms when gluten-sensitive patients encounter small amounts of gluten, and these patients should still follow a gluten-free diet.
AN-PEP is available in the United States in supplement form under several names and is manufactured by the Dutch company DSM. The AN-PEP enzyme used in the study was provided by DSM, but the company provided no other support. Dr. König had no relevant financial conflicts to disclose.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – Gluten-sensitive patients were able to tolerate small amounts of gluten after consuming an enzyme supplement derived from Aspergillus niger as part of a meal in a randomized, placebo-controlled trial of 18 adults. The data were presented at the annual Digestive Disease Week.
The enzyme, A. niger-derived prolyl endoprotease (AN-PEP), has demonstrated the ability to degrade gluten into nonimmunogenic compounds in vivo in healthy subjects, according to Julia König, PhD, of the School of Medical Sciences, Örebro (Sweden) University and her colleagues. The researchers tested the enzyme at two separate doses in 18 adults with self-reported gluten sensitivity.
The participants’ gastric and duodenal content was sampled several times over 180 minutes and analyzed for gluten epitopes using an enzyme-linked immunosorbent assay test. Participants also completed questionnaires after each day of testing.
After taking the enzyme in conjunction with the gluten, stomach gluten content averaged 31 microg x min/mL in the high-dose and low-dose enzyme patients (P = 0.001 for both doses), compared with 281 microg x min/mL in the placebo patients.
By the time the gluten reached the duodenum, the average levels had dropped to 12 microg x min/mL in the high-dose patients (P = 0.019) and 8 microg x min/mL in the low-dose patients (P = 0.015), compared with an average of 65 microg x min/mL in the placebo patients.
Overall, the enzyme was well tolerated by the patients, the researchers said. However, Dr. König emphasized that the enzyme tablet is meant to help avoid symptoms when gluten-sensitive patients encounter small amounts of gluten, and these patients should still follow a gluten-free diet.
AN-PEP is available in the United States in supplement form under several names and is manufactured by the Dutch company DSM. The AN-PEP enzyme used in the study was provided by DSM, but the company provided no other support. Dr. König had no relevant financial conflicts to disclose.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
FROM DDW
Key clinical point: Consuming an enzyme tablet simultaneously with small amounts of gluten may reduce discomfort in gluten-sensitive individuals.
Major finding: On average, gluten levels in the stomach after enzyme consumption were 31 microg x min/mL in both high- and low-dose groups, vs. 281 microg x min/mL in a placebo group.
Data source: A randomized, placebo-controlled trial of 18 gluten-sensitive adults.
Disclosures: The enzyme used in the study, AN-PEP, was provided by the Dutch company DSM, but the company provided no other support. Dr. König had no relevant financial conflicts to disclose.
Genetic test predicts cirrhosis outcomes
CHICAGO – Cirrhosis patients with the rs738409 CG/GG genotype experienced worse outcomes, including a slower recovery of encephalopathy, ascites, and bilirubin, compared with those without this CG/GG genotype, based on data from a prospective study. The findings were presented at the annual Digestive Disease Week.
Most patients with hepatitis C virus–associated cirrhosis do well after treatment with direct-acting antiviral agents to achieve a sustained virologic response, according to Winston Dunn, MD, of Kansas University Medical Center, Kansas City, and his colleagues.
However, patients with decompensated cirrhosis may have a range of outcomes, and, to help predict treatment success, Dr. Dunn and his colleagues examined the possible genetic role of the rs738409 Single Nucleotide Polymorphism of Patatin-like Phospholipase Domain Containing 3 gene.
The researchers assessed 30 adults with Child-Pugh (CPT) Class B or C cirrhosis caused by HCV infection who underwent interferon-free, direct-acting antiviral therapy and achieved sustained virologic response. They collected DNA from each patient using a cheek swab. The study population included 16 patients with a CC genotype, 11 with CG, and 3 with GG.
They measured changes in CPT scores and Model for End-Stage Liver Disease (MELD) scores from before DAA treatment to 12 weeks after treatment. Baseline scores were similar among all patients, as were demographic characteristics, although patients with the rs738409 CC genotype averaged a higher body-mass index 35 kg/m2, vs. 29 kg/m2 (P = 0.03).
After 12 weeks, 13 of 16 patients with the CC genotype (81 %) had improved CPT scores, and 8 patients (50%) had improved MELD scores by at least 1 point. None had worsened CPT or MELD scores. By contrast, 5 of 14 patients with CG/GG genotype (36%) had improved CPT scores, and 4 (29%) had improved MELD scores by at least 1 point; 3 patients (21%) had worsened CPT scores and 4 (29%) had worsened MELD scores by at least 1 point.
Overall, patients in the CG/GG groups showed a 1.7-point higher delta CPT score and a 2.3-point higher delta MELD score after adjusting for confounding variables, compared with patients with CC after adjusting for confounding variables.
The study findings were limited by small numbers and prospective design, and the genetic test is not yet widely available, Dr. Dunn said. However, “Our results will help target patients for liver transplant evaluation based on individual genetic risk factors,” the researchers said.
The study was funded by the Frontiers Pilot and Collaborative Studies Funding Program. Dr. Dunn had no relevant financial conflicts to disclose.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – Cirrhosis patients with the rs738409 CG/GG genotype experienced worse outcomes, including a slower recovery of encephalopathy, ascites, and bilirubin, compared with those without this CG/GG genotype, based on data from a prospective study. The findings were presented at the annual Digestive Disease Week.
Most patients with hepatitis C virus–associated cirrhosis do well after treatment with direct-acting antiviral agents to achieve a sustained virologic response, according to Winston Dunn, MD, of Kansas University Medical Center, Kansas City, and his colleagues.
However, patients with decompensated cirrhosis may have a range of outcomes, and, to help predict treatment success, Dr. Dunn and his colleagues examined the possible genetic role of the rs738409 Single Nucleotide Polymorphism of Patatin-like Phospholipase Domain Containing 3 gene.
The researchers assessed 30 adults with Child-Pugh (CPT) Class B or C cirrhosis caused by HCV infection who underwent interferon-free, direct-acting antiviral therapy and achieved sustained virologic response. They collected DNA from each patient using a cheek swab. The study population included 16 patients with a CC genotype, 11 with CG, and 3 with GG.
They measured changes in CPT scores and Model for End-Stage Liver Disease (MELD) scores from before DAA treatment to 12 weeks after treatment. Baseline scores were similar among all patients, as were demographic characteristics, although patients with the rs738409 CC genotype averaged a higher body-mass index 35 kg/m2, vs. 29 kg/m2 (P = 0.03).
After 12 weeks, 13 of 16 patients with the CC genotype (81 %) had improved CPT scores, and 8 patients (50%) had improved MELD scores by at least 1 point. None had worsened CPT or MELD scores. By contrast, 5 of 14 patients with CG/GG genotype (36%) had improved CPT scores, and 4 (29%) had improved MELD scores by at least 1 point; 3 patients (21%) had worsened CPT scores and 4 (29%) had worsened MELD scores by at least 1 point.
Overall, patients in the CG/GG groups showed a 1.7-point higher delta CPT score and a 2.3-point higher delta MELD score after adjusting for confounding variables, compared with patients with CC after adjusting for confounding variables.
The study findings were limited by small numbers and prospective design, and the genetic test is not yet widely available, Dr. Dunn said. However, “Our results will help target patients for liver transplant evaluation based on individual genetic risk factors,” the researchers said.
The study was funded by the Frontiers Pilot and Collaborative Studies Funding Program. Dr. Dunn had no relevant financial conflicts to disclose.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – Cirrhosis patients with the rs738409 CG/GG genotype experienced worse outcomes, including a slower recovery of encephalopathy, ascites, and bilirubin, compared with those without this CG/GG genotype, based on data from a prospective study. The findings were presented at the annual Digestive Disease Week.
Most patients with hepatitis C virus–associated cirrhosis do well after treatment with direct-acting antiviral agents to achieve a sustained virologic response, according to Winston Dunn, MD, of Kansas University Medical Center, Kansas City, and his colleagues.
However, patients with decompensated cirrhosis may have a range of outcomes, and, to help predict treatment success, Dr. Dunn and his colleagues examined the possible genetic role of the rs738409 Single Nucleotide Polymorphism of Patatin-like Phospholipase Domain Containing 3 gene.
The researchers assessed 30 adults with Child-Pugh (CPT) Class B or C cirrhosis caused by HCV infection who underwent interferon-free, direct-acting antiviral therapy and achieved sustained virologic response. They collected DNA from each patient using a cheek swab. The study population included 16 patients with a CC genotype, 11 with CG, and 3 with GG.
They measured changes in CPT scores and Model for End-Stage Liver Disease (MELD) scores from before DAA treatment to 12 weeks after treatment. Baseline scores were similar among all patients, as were demographic characteristics, although patients with the rs738409 CC genotype averaged a higher body-mass index 35 kg/m2, vs. 29 kg/m2 (P = 0.03).
After 12 weeks, 13 of 16 patients with the CC genotype (81 %) had improved CPT scores, and 8 patients (50%) had improved MELD scores by at least 1 point. None had worsened CPT or MELD scores. By contrast, 5 of 14 patients with CG/GG genotype (36%) had improved CPT scores, and 4 (29%) had improved MELD scores by at least 1 point; 3 patients (21%) had worsened CPT scores and 4 (29%) had worsened MELD scores by at least 1 point.
Overall, patients in the CG/GG groups showed a 1.7-point higher delta CPT score and a 2.3-point higher delta MELD score after adjusting for confounding variables, compared with patients with CC after adjusting for confounding variables.
The study findings were limited by small numbers and prospective design, and the genetic test is not yet widely available, Dr. Dunn said. However, “Our results will help target patients for liver transplant evaluation based on individual genetic risk factors,” the researchers said.
The study was funded by the Frontiers Pilot and Collaborative Studies Funding Program. Dr. Dunn had no relevant financial conflicts to disclose.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
FROM DDW
Key clinical point: Genotyping patients with advanced cirrhosis from HCV could help predict improvement and determine fitness for liver transplants.
Major finding: The rs738409 CG/GG genotype was associated with a 1.7-point higher delta CPT score, a 2.3 -point higher delta MELD score, and slower recovery of encepholpathy, ascites, and bilirubin, compared with those without this CG/GG genotype.
Data source: A prospective study of 35 adults with cirrhosis caused by HCV infection.
Disclosures: The study was funded by the Frontiers Pilot and Collaborative Studies Funding Program.
Drainage may be nonfactor after distal pancreatectomy outcomes
PHILADELPHIA – A randomized multicenter trial that compared patients who had distal pancreatectomy with and without routine peritoneal drainage found no appreciable difference in the complication rates between the two groups, the lead investigator reported at the annual meeting of the American Surgical Association here.
The trial randomized 202 patients to the intraperitoneal drainage group and 197 to the nondrainage group. The groups were well matched in terms of patients who dropped out because of metastatic disease or other reason, as well as demographics and operative data. “They were equally matched for laparoscopic vs. open, equally matched for vascular resection, equally matched for pancreatic texture and duct size, equally matched for method of transection, equally matched for operative time and blood loss and equally matched for surgical pathology,” Dr. Van Buren said.
The primary outcome was frequency of grade 2 complications or greater, which occurred in 44% (76) of the drainage group and 42% (72) of the nondrainage group (P = .804). “Similarly, the groups were equal for grade 3 severe complications as well as median complication severity and median number of complications,” Dr. Van Buren said. The rates of complications of grade 3 or greater were 29% (51) for the drainage group and 26% (44) for the nondrainage group (P = .477). Ninety-day mortality also was similar between the two groups: None died in the drainage group and two (1%) died in the nondrainage group (P = .24).
Drilling down into types of complications, Dr. Van Buren added that rates were similar across the board. “There was no difference in clinically relevant postoperative pancreatic fistula between the drain and no-drain group,” he said. “There was no difference in intra-abdominal abscess, no difference in the rates of postoperative imaging, no difference in the rates of postoperative percutaneous drain placements, and there was no difference in readmission or reoperation.”
One outcome that was noticeably different between the two groups was intra-abdominal fluid collections, reported in 9% (15) of the drainage group and 22% (38) of the nondrainage group (P = .0004). “However,” Dr. Van Buren said, “these were asymptomatic.”
In his discussion of the presentation, Charles Yeo, MD, FACS, of Thomas Jefferson University, Philadelphia, said that “the scope and the rigor of this study are impressive and quite laudable” but raised a number of questions, including concerns about the two deaths in the nondrainage group in the context of two other trials: a smaller multicenter trial, coauthored by Dr. Van Buren, that compared postoperative use of drains and nondrainage in pancreaticoduodenectomy but was halted because of eight deaths in the nondrainage group (Ann Surg. 2014;259:605-12); and the German PANDRA trial reported at last year’s ASA meeting that found nondrainage after pancreaticoduodenectomy to be superior to drainage in terms of reintervention and fistula rates.
Dr. Van Buren replied that the first study from Baylor – referenced by Dr. Yeo – involved “well-balanced groups, and they were equally matched and had minimal dropout throughout.” Because of that, the finding that drain placement for the pancreaticoduodenectomy “was definitive,” whereas the PANDRA trial was subject to some criticisms. The screening and randomization processes in PANDRA have been criticized because 3,200 patients were eligible for enrollment, suggesting a screening bias, Dr. Van Buren said. In addition, drains were placed in 21% of patients who were allocated to the no-drain group, suggesting surgeons deviated from the protocol in higher-risk situations, resulting in additional selection bias. This implies PANDRA was more of a selective draining trial, he said.
Dr. Van Buren and Dr. Yeo reported having no financial disclosures.
The complete manuscript of this study and its presentation at the American Surgical Association’s 137th Annual Meeting, April 2017, in Philadelphia, is to be published in Annals of Surgery pending editorial review.
PHILADELPHIA – A randomized multicenter trial that compared patients who had distal pancreatectomy with and without routine peritoneal drainage found no appreciable difference in the complication rates between the two groups, the lead investigator reported at the annual meeting of the American Surgical Association here.
The trial randomized 202 patients to the intraperitoneal drainage group and 197 to the nondrainage group. The groups were well matched in terms of patients who dropped out because of metastatic disease or other reason, as well as demographics and operative data. “They were equally matched for laparoscopic vs. open, equally matched for vascular resection, equally matched for pancreatic texture and duct size, equally matched for method of transection, equally matched for operative time and blood loss and equally matched for surgical pathology,” Dr. Van Buren said.
The primary outcome was frequency of grade 2 complications or greater, which occurred in 44% (76) of the drainage group and 42% (72) of the nondrainage group (P = .804). “Similarly, the groups were equal for grade 3 severe complications as well as median complication severity and median number of complications,” Dr. Van Buren said. The rates of complications of grade 3 or greater were 29% (51) for the drainage group and 26% (44) for the nondrainage group (P = .477). Ninety-day mortality also was similar between the two groups: None died in the drainage group and two (1%) died in the nondrainage group (P = .24).
Drilling down into types of complications, Dr. Van Buren added that rates were similar across the board. “There was no difference in clinically relevant postoperative pancreatic fistula between the drain and no-drain group,” he said. “There was no difference in intra-abdominal abscess, no difference in the rates of postoperative imaging, no difference in the rates of postoperative percutaneous drain placements, and there was no difference in readmission or reoperation.”
One outcome that was noticeably different between the two groups was intra-abdominal fluid collections, reported in 9% (15) of the drainage group and 22% (38) of the nondrainage group (P = .0004). “However,” Dr. Van Buren said, “these were asymptomatic.”
In his discussion of the presentation, Charles Yeo, MD, FACS, of Thomas Jefferson University, Philadelphia, said that “the scope and the rigor of this study are impressive and quite laudable” but raised a number of questions, including concerns about the two deaths in the nondrainage group in the context of two other trials: a smaller multicenter trial, coauthored by Dr. Van Buren, that compared postoperative use of drains and nondrainage in pancreaticoduodenectomy but was halted because of eight deaths in the nondrainage group (Ann Surg. 2014;259:605-12); and the German PANDRA trial reported at last year’s ASA meeting that found nondrainage after pancreaticoduodenectomy to be superior to drainage in terms of reintervention and fistula rates.
Dr. Van Buren replied that the first study from Baylor – referenced by Dr. Yeo – involved “well-balanced groups, and they were equally matched and had minimal dropout throughout.” Because of that, the finding that drain placement for the pancreaticoduodenectomy “was definitive,” whereas the PANDRA trial was subject to some criticisms. The screening and randomization processes in PANDRA have been criticized because 3,200 patients were eligible for enrollment, suggesting a screening bias, Dr. Van Buren said. In addition, drains were placed in 21% of patients who were allocated to the no-drain group, suggesting surgeons deviated from the protocol in higher-risk situations, resulting in additional selection bias. This implies PANDRA was more of a selective draining trial, he said.
Dr. Van Buren and Dr. Yeo reported having no financial disclosures.
The complete manuscript of this study and its presentation at the American Surgical Association’s 137th Annual Meeting, April 2017, in Philadelphia, is to be published in Annals of Surgery pending editorial review.
PHILADELPHIA – A randomized multicenter trial that compared patients who had distal pancreatectomy with and without routine peritoneal drainage found no appreciable difference in the complication rates between the two groups, the lead investigator reported at the annual meeting of the American Surgical Association here.
The trial randomized 202 patients to the intraperitoneal drainage group and 197 to the nondrainage group. The groups were well matched in terms of patients who dropped out because of metastatic disease or other reason, as well as demographics and operative data. “They were equally matched for laparoscopic vs. open, equally matched for vascular resection, equally matched for pancreatic texture and duct size, equally matched for method of transection, equally matched for operative time and blood loss and equally matched for surgical pathology,” Dr. Van Buren said.
The primary outcome was frequency of grade 2 complications or greater, which occurred in 44% (76) of the drainage group and 42% (72) of the nondrainage group (P = .804). “Similarly, the groups were equal for grade 3 severe complications as well as median complication severity and median number of complications,” Dr. Van Buren said. The rates of complications of grade 3 or greater were 29% (51) for the drainage group and 26% (44) for the nondrainage group (P = .477). Ninety-day mortality also was similar between the two groups: None died in the drainage group and two (1%) died in the nondrainage group (P = .24).
Drilling down into types of complications, Dr. Van Buren added that rates were similar across the board. “There was no difference in clinically relevant postoperative pancreatic fistula between the drain and no-drain group,” he said. “There was no difference in intra-abdominal abscess, no difference in the rates of postoperative imaging, no difference in the rates of postoperative percutaneous drain placements, and there was no difference in readmission or reoperation.”
One outcome that was noticeably different between the two groups was intra-abdominal fluid collections, reported in 9% (15) of the drainage group and 22% (38) of the nondrainage group (P = .0004). “However,” Dr. Van Buren said, “these were asymptomatic.”
In his discussion of the presentation, Charles Yeo, MD, FACS, of Thomas Jefferson University, Philadelphia, said that “the scope and the rigor of this study are impressive and quite laudable” but raised a number of questions, including concerns about the two deaths in the nondrainage group in the context of two other trials: a smaller multicenter trial, coauthored by Dr. Van Buren, that compared postoperative use of drains and nondrainage in pancreaticoduodenectomy but was halted because of eight deaths in the nondrainage group (Ann Surg. 2014;259:605-12); and the German PANDRA trial reported at last year’s ASA meeting that found nondrainage after pancreaticoduodenectomy to be superior to drainage in terms of reintervention and fistula rates.
Dr. Van Buren replied that the first study from Baylor – referenced by Dr. Yeo – involved “well-balanced groups, and they were equally matched and had minimal dropout throughout.” Because of that, the finding that drain placement for the pancreaticoduodenectomy “was definitive,” whereas the PANDRA trial was subject to some criticisms. The screening and randomization processes in PANDRA have been criticized because 3,200 patients were eligible for enrollment, suggesting a screening bias, Dr. Van Buren said. In addition, drains were placed in 21% of patients who were allocated to the no-drain group, suggesting surgeons deviated from the protocol in higher-risk situations, resulting in additional selection bias. This implies PANDRA was more of a selective draining trial, he said.
Dr. Van Buren and Dr. Yeo reported having no financial disclosures.
The complete manuscript of this study and its presentation at the American Surgical Association’s 137th Annual Meeting, April 2017, in Philadelphia, is to be published in Annals of Surgery pending editorial review.
AT THE ASA ANNUAL
Key clinical point: A randomized clinical trial has provided Level 1 evidence that placement of intraperitoneal drains does not alter clinical outcomes after distal pancreatectomy.
Major finding: No significant difference was found in the rate of complications between those who had drains and those who did not (44% vs. 42% of complications greater than grade 2).
Data source: Randomized trial of 399 patients who underwent distal pancreatectomy at 14 high-volume pancreas centers.
Disclosures: Dr. Van Buren reported having no financial disclosures.
VIDEO: Bile acid malabsorption as a cause of chronic diarrhea
CHICAGO – Bile acid malabsorption increasingly is recognized as a cause of persistent, chronic diarrhea, but patients often receive suboptimal treatment because medical and public awareness is low, Julian Walters, MD, of Imperial College London, said at Digestive Disease Week®.
Members of two patient support groups in the United Kingdom were invited to complete an online survey to provide information on how this condition affects them. The first 100 responses were analyzed. The majority of respondents were female (91). More than 35 respondents were diagnosed after the age of 50 years, and 35 felt their condition had not been taken seriously by multiple practitioners prior to their eventual diagnosis, Dr. Walters reported.
Two-thirds of respondents had been diagnosed with irritable bowel syndrome; the majority (68) of these had more than 10 interactions with medical professionals before being diagnosed with bile acid malabsorption.
Once appropriately diagnosed, most respondents reported doing very well on drugs such as cholestyramine and colesevelam, Dr. Walters said. He stressed that mental health issues are an important part of this condition because of its pervasive effects on daily life.
He discusses the survey and bile acid malabsorption in this video interview.
Dr. Walters disclosed that he has been a consultant to or has received research funds from GE Healthcare, Intercept, Albireo, and Novartis.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – Bile acid malabsorption increasingly is recognized as a cause of persistent, chronic diarrhea, but patients often receive suboptimal treatment because medical and public awareness is low, Julian Walters, MD, of Imperial College London, said at Digestive Disease Week®.
Members of two patient support groups in the United Kingdom were invited to complete an online survey to provide information on how this condition affects them. The first 100 responses were analyzed. The majority of respondents were female (91). More than 35 respondents were diagnosed after the age of 50 years, and 35 felt their condition had not been taken seriously by multiple practitioners prior to their eventual diagnosis, Dr. Walters reported.
Two-thirds of respondents had been diagnosed with irritable bowel syndrome; the majority (68) of these had more than 10 interactions with medical professionals before being diagnosed with bile acid malabsorption.
Once appropriately diagnosed, most respondents reported doing very well on drugs such as cholestyramine and colesevelam, Dr. Walters said. He stressed that mental health issues are an important part of this condition because of its pervasive effects on daily life.
He discusses the survey and bile acid malabsorption in this video interview.
Dr. Walters disclosed that he has been a consultant to or has received research funds from GE Healthcare, Intercept, Albireo, and Novartis.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – Bile acid malabsorption increasingly is recognized as a cause of persistent, chronic diarrhea, but patients often receive suboptimal treatment because medical and public awareness is low, Julian Walters, MD, of Imperial College London, said at Digestive Disease Week®.
Members of two patient support groups in the United Kingdom were invited to complete an online survey to provide information on how this condition affects them. The first 100 responses were analyzed. The majority of respondents were female (91). More than 35 respondents were diagnosed after the age of 50 years, and 35 felt their condition had not been taken seriously by multiple practitioners prior to their eventual diagnosis, Dr. Walters reported.
Two-thirds of respondents had been diagnosed with irritable bowel syndrome; the majority (68) of these had more than 10 interactions with medical professionals before being diagnosed with bile acid malabsorption.
Once appropriately diagnosed, most respondents reported doing very well on drugs such as cholestyramine and colesevelam, Dr. Walters said. He stressed that mental health issues are an important part of this condition because of its pervasive effects on daily life.
He discusses the survey and bile acid malabsorption in this video interview.
Dr. Walters disclosed that he has been a consultant to or has received research funds from GE Healthcare, Intercept, Albireo, and Novartis.
Digestive Disease Week® is jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
AT DDW
PATH study: Subcutaneous immunoglobulin safe, effective for CIDP maintenance
BOSTON – Subcutaneously administered immunoglobulin was effective, well tolerated, and preferred over intravenous administration as maintenance treatment for chronic inflammatory demyelinating polyneuropathy in the phase III, randomized, placebo-controlled PATH study.
The 172-patient trial tested a high and low dose of subcutaneous immunoglobulin (SCIg) over the course of 25 weeks to determine their effect on the primary outcome of chronic inflammatory demyelinating polyneuropathy (CIDP) relapse or withdrawal from treatment for any reason. In this evaluation of using SCIg for maintenance of response, relapses or treatment withdrawal occurred in 63% with placebo, 39% with low dose SCIg (0.2 g/kg weekly), and 33% with high dose (0.4 g/kg weekly), Ivo N. van Schaik, MD, reported at the annual meeting of the American Academy of Neurology.
Patients in the trial had received at lease one dose of intravenous immunoglobulin (IVIg) within 8 weeks before screening. They then underwent a screening period first, followed by an IgG dependency period of up to 12 weeks to test for ongoing need for IgG. The patients who experienced CIDP relapse during this test period were administered a standardized IVIG regimen during a 10- to 13-week restabilization period, and those who improved and maintained their Inflammatory Neuropathy Cause and Treatment (INCAT) score continued to the randomized subcutaneous treatment period of the study.
CIDP relapse occurred in 56% of patients in the placebo group, compared with 33% in the low- and 19% in the high-dose SCIg groups, said Dr. van Schaik of the University of Amsterdam (the Netherlands).
“Both [SCIg] doses were effective in preventing relapse. The higher dose performed better than the lower dose, but the difference was not statistically significant,” he said.
Both doses were significantly more effective than placebo.
Study participants were adults with definite or probable CIDP enrolled from 69 neuromuscular centers worldwide between March 2012 and November 2015. Weekly self-administered subcutaneous infusions of SCIg (IgPro20Hizentra) were performed during 1 or 2 consecutive days in two separate sessions using special infusion pumps. Patients reported that learning the self-administration technique was easy, Dr. van Schaik said.
Adverse effects included mainly local reactions, which occurred in 19% of patients, but these were generally mild and rarely resulted in therapy discontinuation, and local reactions decreased considerably over time, he said, noting that systemic effects are reduced with SCIg vs. IVIg.
Subcutaneous administration of immunoglobulin is not new. In fact, it has been used successfully in patients with immunodeficiency syndromes for more than 2 decades and can increase patient autonomy and reduce costs by reducing hospital and infusion center visits, but this is the first study to assess efficacy, safety, and tolerability of this approach in an adequately powered, randomized, clinical trial, he said.
“Subcutaneous immunoglobulin can be used ... for maintenance treatment of patients with CIDP,” he concluded, adding that weekly doses of 0.2-0.4 g/kg are supported by these data, and that maintenance doses should be individualized based on patient factors and previous IVIg dose and frequency.
The PATH study was sponsored by CSL-Behring. Dr. van Schaik chairs a steering committee for CSL-Behring and received departmental honoraria for serving on scientific advisory boards for CSL-Behring, Baxalta, and UCB. He also received speakers fees from CSL-Behring and Kedrion.
BOSTON – Subcutaneously administered immunoglobulin was effective, well tolerated, and preferred over intravenous administration as maintenance treatment for chronic inflammatory demyelinating polyneuropathy in the phase III, randomized, placebo-controlled PATH study.
The 172-patient trial tested a high and low dose of subcutaneous immunoglobulin (SCIg) over the course of 25 weeks to determine their effect on the primary outcome of chronic inflammatory demyelinating polyneuropathy (CIDP) relapse or withdrawal from treatment for any reason. In this evaluation of using SCIg for maintenance of response, relapses or treatment withdrawal occurred in 63% with placebo, 39% with low dose SCIg (0.2 g/kg weekly), and 33% with high dose (0.4 g/kg weekly), Ivo N. van Schaik, MD, reported at the annual meeting of the American Academy of Neurology.
Patients in the trial had received at lease one dose of intravenous immunoglobulin (IVIg) within 8 weeks before screening. They then underwent a screening period first, followed by an IgG dependency period of up to 12 weeks to test for ongoing need for IgG. The patients who experienced CIDP relapse during this test period were administered a standardized IVIG regimen during a 10- to 13-week restabilization period, and those who improved and maintained their Inflammatory Neuropathy Cause and Treatment (INCAT) score continued to the randomized subcutaneous treatment period of the study.
CIDP relapse occurred in 56% of patients in the placebo group, compared with 33% in the low- and 19% in the high-dose SCIg groups, said Dr. van Schaik of the University of Amsterdam (the Netherlands).
“Both [SCIg] doses were effective in preventing relapse. The higher dose performed better than the lower dose, but the difference was not statistically significant,” he said.
Both doses were significantly more effective than placebo.
Study participants were adults with definite or probable CIDP enrolled from 69 neuromuscular centers worldwide between March 2012 and November 2015. Weekly self-administered subcutaneous infusions of SCIg (IgPro20Hizentra) were performed during 1 or 2 consecutive days in two separate sessions using special infusion pumps. Patients reported that learning the self-administration technique was easy, Dr. van Schaik said.
Adverse effects included mainly local reactions, which occurred in 19% of patients, but these were generally mild and rarely resulted in therapy discontinuation, and local reactions decreased considerably over time, he said, noting that systemic effects are reduced with SCIg vs. IVIg.
Subcutaneous administration of immunoglobulin is not new. In fact, it has been used successfully in patients with immunodeficiency syndromes for more than 2 decades and can increase patient autonomy and reduce costs by reducing hospital and infusion center visits, but this is the first study to assess efficacy, safety, and tolerability of this approach in an adequately powered, randomized, clinical trial, he said.
“Subcutaneous immunoglobulin can be used ... for maintenance treatment of patients with CIDP,” he concluded, adding that weekly doses of 0.2-0.4 g/kg are supported by these data, and that maintenance doses should be individualized based on patient factors and previous IVIg dose and frequency.
The PATH study was sponsored by CSL-Behring. Dr. van Schaik chairs a steering committee for CSL-Behring and received departmental honoraria for serving on scientific advisory boards for CSL-Behring, Baxalta, and UCB. He also received speakers fees from CSL-Behring and Kedrion.
BOSTON – Subcutaneously administered immunoglobulin was effective, well tolerated, and preferred over intravenous administration as maintenance treatment for chronic inflammatory demyelinating polyneuropathy in the phase III, randomized, placebo-controlled PATH study.
The 172-patient trial tested a high and low dose of subcutaneous immunoglobulin (SCIg) over the course of 25 weeks to determine their effect on the primary outcome of chronic inflammatory demyelinating polyneuropathy (CIDP) relapse or withdrawal from treatment for any reason. In this evaluation of using SCIg for maintenance of response, relapses or treatment withdrawal occurred in 63% with placebo, 39% with low dose SCIg (0.2 g/kg weekly), and 33% with high dose (0.4 g/kg weekly), Ivo N. van Schaik, MD, reported at the annual meeting of the American Academy of Neurology.
Patients in the trial had received at lease one dose of intravenous immunoglobulin (IVIg) within 8 weeks before screening. They then underwent a screening period first, followed by an IgG dependency period of up to 12 weeks to test for ongoing need for IgG. The patients who experienced CIDP relapse during this test period were administered a standardized IVIG regimen during a 10- to 13-week restabilization period, and those who improved and maintained their Inflammatory Neuropathy Cause and Treatment (INCAT) score continued to the randomized subcutaneous treatment period of the study.
CIDP relapse occurred in 56% of patients in the placebo group, compared with 33% in the low- and 19% in the high-dose SCIg groups, said Dr. van Schaik of the University of Amsterdam (the Netherlands).
“Both [SCIg] doses were effective in preventing relapse. The higher dose performed better than the lower dose, but the difference was not statistically significant,” he said.
Both doses were significantly more effective than placebo.
Study participants were adults with definite or probable CIDP enrolled from 69 neuromuscular centers worldwide between March 2012 and November 2015. Weekly self-administered subcutaneous infusions of SCIg (IgPro20Hizentra) were performed during 1 or 2 consecutive days in two separate sessions using special infusion pumps. Patients reported that learning the self-administration technique was easy, Dr. van Schaik said.
Adverse effects included mainly local reactions, which occurred in 19% of patients, but these were generally mild and rarely resulted in therapy discontinuation, and local reactions decreased considerably over time, he said, noting that systemic effects are reduced with SCIg vs. IVIg.
Subcutaneous administration of immunoglobulin is not new. In fact, it has been used successfully in patients with immunodeficiency syndromes for more than 2 decades and can increase patient autonomy and reduce costs by reducing hospital and infusion center visits, but this is the first study to assess efficacy, safety, and tolerability of this approach in an adequately powered, randomized, clinical trial, he said.
“Subcutaneous immunoglobulin can be used ... for maintenance treatment of patients with CIDP,” he concluded, adding that weekly doses of 0.2-0.4 g/kg are supported by these data, and that maintenance doses should be individualized based on patient factors and previous IVIg dose and frequency.
The PATH study was sponsored by CSL-Behring. Dr. van Schaik chairs a steering committee for CSL-Behring and received departmental honoraria for serving on scientific advisory boards for CSL-Behring, Baxalta, and UCB. He also received speakers fees from CSL-Behring and Kedrion.
Key clinical point:
Major finding: CIDP relapse occurred in 56% of patients in the placebo group, compared with 33% in the low- and 19% in the high-dose SCIg groups.
Data source: The randomized, placebo-controlled phase III PATH study of 172 CIDP patients.
Disclosures: The PATH study was sponsored by CSL-Behring. Dr. van Schaik chairs a steering committee for CSL-Behring and received departmental honoraria for serving on scientific advisory boards for CSL-Behring, Baxalta, and UCB. He also received speakers fees from CSL-Behring and Kedrion.
Flu shots may spark immune adverse events in PD-1 blockade for NSCLC
GENEVA – The influenza vaccine may interact with immune checkpoint inhibitors in patients with lung cancer, results of a small study suggest.
Among 23 patients with non–small cell lung cancer (NSCLC) treated with a drug targeted against programmed death-1 (PD-1), the seasonal flu vaccine appeared to produce good serologic protection against infection, but at the possible cost of an increase in the rate of immune-related adverse events (IrAE), reported Sacha Rothschild, MD, PhD, of University Hospital Basel (Switzerland) at the European Lung Cancer Conference.
Among 23 patients with lung cancer treated with a PD-1 inhibitor, 12 (52.2%) had one or more IrAEs. In contrast, the most frequent IrAE in a key registration trial for nivolumab (Opdivo) was skin rash, which occurred in 9% of patients (N Engl J Med. 2015 Jul 9;373:1627-39).
“It’s a very small study, but it raises some concern that there might be an interaction between the vaccine and PD-1 blockade,” Dr. Rothschild said.
To see whether blocking the PD-1/PD–ligand-1 (PD-L1) axis might induce an overactive immune response, the investigators prospectively studied 23 patients with NSCLC who were undergoing treatment with a PD-1 inhibitor – 22 with nivolumab and 1 with pembrolizumab (Keytruda) – who were also vaccinated with a trivalent influenza vaccine in October or November 2015. They used the partners of the patients, also vaccinated, for an age-matched cohort of healthy controls.
The investigators looked at antibody titers against flu strains covered by the vaccine, measured inflammatory chemokines and assessed the vaccine’s safety and the frequency of IrAEs.
None of the patients came down with the flu during the 2015-2016 season. There were no major differences over time in the generation of antibodies against all three viral strains tested.
However, at both 30 and 60 days after vaccination, a hemagglutination inhibition assay showed slightly elevated antibody titers among patients, compared with controls. Antibody titers against H1N1 virus also appeared to increase somewhat more rapidly among patients than among controls, the authors found.
The patients appeared to tolerate the vaccine well, and no serious adverse events were reported within 30 days of vaccination.
When they looked at the incidence of IrAEs, however, the investigators found that six patients had grade 1 or 2 IrAEs, and six had grade 3 or 4 events.
The events included skin rash and arthritis in three patients each, colitis and encephalitis in two patients each, and hypothyroidism, pneumonitis, and neuropathy in one patient each.
“We looked into inflammatory chemokines to understand if there was a high rate of systemic inflammation, and we didn’t find any differences in this regard. So far, we have no clue about why the immune-related adverse event rate in this group is higher,” Dr. Rothschild said.
Although the sample size was small, the IrAE effect they saw was large enough to warrant concern, and it should be studied in a larger population sample, he said.
Egbert Smit, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, who was not involved in the study, commented that “it shows how much we still have to learn about the optimal use of checkpoint inhibitors in lung cancer patients. The study is important as it is the first to investigate the impact of influenza vaccination in such patients, and there is a hint that we actually put them at increased risk for serious toxicities, including encephalitis. However, until we have data on a larger cohort, preferably in a controlled, prospective study, in my institution, we advocate influenza vaccination irrespective of concurrent treatment with immune-checkpoint inhibitors.”
The study was supported by institutional funding. The investigators and Dr. Smit reported no relevant conflicts of interest.
GENEVA – The influenza vaccine may interact with immune checkpoint inhibitors in patients with lung cancer, results of a small study suggest.
Among 23 patients with non–small cell lung cancer (NSCLC) treated with a drug targeted against programmed death-1 (PD-1), the seasonal flu vaccine appeared to produce good serologic protection against infection, but at the possible cost of an increase in the rate of immune-related adverse events (IrAE), reported Sacha Rothschild, MD, PhD, of University Hospital Basel (Switzerland) at the European Lung Cancer Conference.
Among 23 patients with lung cancer treated with a PD-1 inhibitor, 12 (52.2%) had one or more IrAEs. In contrast, the most frequent IrAE in a key registration trial for nivolumab (Opdivo) was skin rash, which occurred in 9% of patients (N Engl J Med. 2015 Jul 9;373:1627-39).
“It’s a very small study, but it raises some concern that there might be an interaction between the vaccine and PD-1 blockade,” Dr. Rothschild said.
To see whether blocking the PD-1/PD–ligand-1 (PD-L1) axis might induce an overactive immune response, the investigators prospectively studied 23 patients with NSCLC who were undergoing treatment with a PD-1 inhibitor – 22 with nivolumab and 1 with pembrolizumab (Keytruda) – who were also vaccinated with a trivalent influenza vaccine in October or November 2015. They used the partners of the patients, also vaccinated, for an age-matched cohort of healthy controls.
The investigators looked at antibody titers against flu strains covered by the vaccine, measured inflammatory chemokines and assessed the vaccine’s safety and the frequency of IrAEs.
None of the patients came down with the flu during the 2015-2016 season. There were no major differences over time in the generation of antibodies against all three viral strains tested.
However, at both 30 and 60 days after vaccination, a hemagglutination inhibition assay showed slightly elevated antibody titers among patients, compared with controls. Antibody titers against H1N1 virus also appeared to increase somewhat more rapidly among patients than among controls, the authors found.
The patients appeared to tolerate the vaccine well, and no serious adverse events were reported within 30 days of vaccination.
When they looked at the incidence of IrAEs, however, the investigators found that six patients had grade 1 or 2 IrAEs, and six had grade 3 or 4 events.
The events included skin rash and arthritis in three patients each, colitis and encephalitis in two patients each, and hypothyroidism, pneumonitis, and neuropathy in one patient each.
“We looked into inflammatory chemokines to understand if there was a high rate of systemic inflammation, and we didn’t find any differences in this regard. So far, we have no clue about why the immune-related adverse event rate in this group is higher,” Dr. Rothschild said.
Although the sample size was small, the IrAE effect they saw was large enough to warrant concern, and it should be studied in a larger population sample, he said.
Egbert Smit, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, who was not involved in the study, commented that “it shows how much we still have to learn about the optimal use of checkpoint inhibitors in lung cancer patients. The study is important as it is the first to investigate the impact of influenza vaccination in such patients, and there is a hint that we actually put them at increased risk for serious toxicities, including encephalitis. However, until we have data on a larger cohort, preferably in a controlled, prospective study, in my institution, we advocate influenza vaccination irrespective of concurrent treatment with immune-checkpoint inhibitors.”
The study was supported by institutional funding. The investigators and Dr. Smit reported no relevant conflicts of interest.
GENEVA – The influenza vaccine may interact with immune checkpoint inhibitors in patients with lung cancer, results of a small study suggest.
Among 23 patients with non–small cell lung cancer (NSCLC) treated with a drug targeted against programmed death-1 (PD-1), the seasonal flu vaccine appeared to produce good serologic protection against infection, but at the possible cost of an increase in the rate of immune-related adverse events (IrAE), reported Sacha Rothschild, MD, PhD, of University Hospital Basel (Switzerland) at the European Lung Cancer Conference.
Among 23 patients with lung cancer treated with a PD-1 inhibitor, 12 (52.2%) had one or more IrAEs. In contrast, the most frequent IrAE in a key registration trial for nivolumab (Opdivo) was skin rash, which occurred in 9% of patients (N Engl J Med. 2015 Jul 9;373:1627-39).
“It’s a very small study, but it raises some concern that there might be an interaction between the vaccine and PD-1 blockade,” Dr. Rothschild said.
To see whether blocking the PD-1/PD–ligand-1 (PD-L1) axis might induce an overactive immune response, the investigators prospectively studied 23 patients with NSCLC who were undergoing treatment with a PD-1 inhibitor – 22 with nivolumab and 1 with pembrolizumab (Keytruda) – who were also vaccinated with a trivalent influenza vaccine in October or November 2015. They used the partners of the patients, also vaccinated, for an age-matched cohort of healthy controls.
The investigators looked at antibody titers against flu strains covered by the vaccine, measured inflammatory chemokines and assessed the vaccine’s safety and the frequency of IrAEs.
None of the patients came down with the flu during the 2015-2016 season. There were no major differences over time in the generation of antibodies against all three viral strains tested.
However, at both 30 and 60 days after vaccination, a hemagglutination inhibition assay showed slightly elevated antibody titers among patients, compared with controls. Antibody titers against H1N1 virus also appeared to increase somewhat more rapidly among patients than among controls, the authors found.
The patients appeared to tolerate the vaccine well, and no serious adverse events were reported within 30 days of vaccination.
When they looked at the incidence of IrAEs, however, the investigators found that six patients had grade 1 or 2 IrAEs, and six had grade 3 or 4 events.
The events included skin rash and arthritis in three patients each, colitis and encephalitis in two patients each, and hypothyroidism, pneumonitis, and neuropathy in one patient each.
“We looked into inflammatory chemokines to understand if there was a high rate of systemic inflammation, and we didn’t find any differences in this regard. So far, we have no clue about why the immune-related adverse event rate in this group is higher,” Dr. Rothschild said.
Although the sample size was small, the IrAE effect they saw was large enough to warrant concern, and it should be studied in a larger population sample, he said.
Egbert Smit, MD, PhD, of the Netherlands Cancer Institute in Amsterdam, who was not involved in the study, commented that “it shows how much we still have to learn about the optimal use of checkpoint inhibitors in lung cancer patients. The study is important as it is the first to investigate the impact of influenza vaccination in such patients, and there is a hint that we actually put them at increased risk for serious toxicities, including encephalitis. However, until we have data on a larger cohort, preferably in a controlled, prospective study, in my institution, we advocate influenza vaccination irrespective of concurrent treatment with immune-checkpoint inhibitors.”
The study was supported by institutional funding. The investigators and Dr. Smit reported no relevant conflicts of interest.
AT ELCC
Key clinical point:
Major finding: Of 23 patients who were vaccinated, 12 developed IrAEs, including 6 grade 1/2 and 6 grade 3/4 events.
Data source: Prospective study of 23 patients with NSCLC and 23 healthy controls.
Disclosures: The study was supported by institutional funding. The investigators reported no relevant conflicts of interest.
PRAC finds insufficient evidence of difference between FVIII products
There is no “clear and consistent evidence” that hemophilia A patients are more likely to develop inhibitors if they receive a recombinant factor VIII (FVIII) product rather than a plasma-derived FVIII product, according to the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC).
The PRAC conducted a review of FVIII products to evaluate the risk of inhibitor development in patients with hemophilia A who had not previously received FVIII treatment.
The review covered all FVIII products authorized for use in the European Union. This includes products containing the active substances human coagulation factor VIII, efmoroctocog alfa, moroctocog alfa, octocog alfa, simoctocog alfa, susoctocog alfa, and turoctocog alfa.
The review was started after publication of the SIPPET study, which indicated that inhibitors occur more frequently in patients receiving FVIII products made by recombinant DNA technology rather than FVIII products derived from plasma.
The PRAC’s review also covered other relevant studies, including interventional clinical trials and observational studies.
The studies reviewed differed in their design, patient populations, and findings, and the PRAC concluded that they did not provide clear evidence of a difference in the risk of inhibitor development between the 2 classes of FVIII products.
In addition, due to the different characteristics of individual products within the 2 classes, the PRAC considered that evaluation of the risk of inhibitor development should be at the product level instead of at the class level.
The risk for each individual product will continue to be assessed as more evidence becomes available.
The PRAC recommended that prescribing information be updated to reflect the current evidence. The update should include, as appropriate, listing of the development of inhibitors as a very common side effect in previously untreated patients and as an uncommon side effect in previously treated patients.
The existing warning on inhibitor development should be amended to highlight that the presence of low levels of inhibitors poses less of a risk of severe bleeding than high levels.
The PRAC’s recommendation will be sent to the EMA’s Committee for Medicinal Products for Human Use (CHMP) for the adoption of the EMA’s final opinion. Further details and information for patients and healthcare professionals will be published at the time of the CHMP opinion.
The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all European Union member states. 
There is no “clear and consistent evidence” that hemophilia A patients are more likely to develop inhibitors if they receive a recombinant factor VIII (FVIII) product rather than a plasma-derived FVIII product, according to the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC).
The PRAC conducted a review of FVIII products to evaluate the risk of inhibitor development in patients with hemophilia A who had not previously received FVIII treatment.
The review covered all FVIII products authorized for use in the European Union. This includes products containing the active substances human coagulation factor VIII, efmoroctocog alfa, moroctocog alfa, octocog alfa, simoctocog alfa, susoctocog alfa, and turoctocog alfa.
The review was started after publication of the SIPPET study, which indicated that inhibitors occur more frequently in patients receiving FVIII products made by recombinant DNA technology rather than FVIII products derived from plasma.
The PRAC’s review also covered other relevant studies, including interventional clinical trials and observational studies.
The studies reviewed differed in their design, patient populations, and findings, and the PRAC concluded that they did not provide clear evidence of a difference in the risk of inhibitor development between the 2 classes of FVIII products.
In addition, due to the different characteristics of individual products within the 2 classes, the PRAC considered that evaluation of the risk of inhibitor development should be at the product level instead of at the class level.
The risk for each individual product will continue to be assessed as more evidence becomes available.
The PRAC recommended that prescribing information be updated to reflect the current evidence. The update should include, as appropriate, listing of the development of inhibitors as a very common side effect in previously untreated patients and as an uncommon side effect in previously treated patients.
The existing warning on inhibitor development should be amended to highlight that the presence of low levels of inhibitors poses less of a risk of severe bleeding than high levels.
The PRAC’s recommendation will be sent to the EMA’s Committee for Medicinal Products for Human Use (CHMP) for the adoption of the EMA’s final opinion. Further details and information for patients and healthcare professionals will be published at the time of the CHMP opinion.
The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all European Union member states.
There is no “clear and consistent evidence” that hemophilia A patients are more likely to develop inhibitors if they receive a recombinant factor VIII (FVIII) product rather than a plasma-derived FVIII product, according to the European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC).
The PRAC conducted a review of FVIII products to evaluate the risk of inhibitor development in patients with hemophilia A who had not previously received FVIII treatment.
The review covered all FVIII products authorized for use in the European Union. This includes products containing the active substances human coagulation factor VIII, efmoroctocog alfa, moroctocog alfa, octocog alfa, simoctocog alfa, susoctocog alfa, and turoctocog alfa.
The review was started after publication of the SIPPET study, which indicated that inhibitors occur more frequently in patients receiving FVIII products made by recombinant DNA technology rather than FVIII products derived from plasma.
The PRAC’s review also covered other relevant studies, including interventional clinical trials and observational studies.
The studies reviewed differed in their design, patient populations, and findings, and the PRAC concluded that they did not provide clear evidence of a difference in the risk of inhibitor development between the 2 classes of FVIII products.
In addition, due to the different characteristics of individual products within the 2 classes, the PRAC considered that evaluation of the risk of inhibitor development should be at the product level instead of at the class level.
The risk for each individual product will continue to be assessed as more evidence becomes available.
The PRAC recommended that prescribing information be updated to reflect the current evidence. The update should include, as appropriate, listing of the development of inhibitors as a very common side effect in previously untreated patients and as an uncommon side effect in previously treated patients.
The existing warning on inhibitor development should be amended to highlight that the presence of low levels of inhibitors poses less of a risk of severe bleeding than high levels.
The PRAC’s recommendation will be sent to the EMA’s Committee for Medicinal Products for Human Use (CHMP) for the adoption of the EMA’s final opinion. Further details and information for patients and healthcare professionals will be published at the time of the CHMP opinion.
The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all European Union member states.