Richard Mark Kirkner

NEW YORK – Aortic aneurysm ranks as one of the top 20 causes of death in the United States. Most of these aneurysms are clinically silent until they rupture, but Yale cardiovascular surgeon John A. Elefteriades, MD, has developed a clinical paradigm that identifies eight markers that physicians can use to detect the disease before it strikes.

Dr. Elefteriades calls his paradigm “Guilt by Association.” It is based on an article he published online last year in the journal Open Heart (2015;2:e000169).

“What we need is for our colleagues in affiliated disciplines to recognize the importance of these offenders in indicating the presence of thoracic aortic aneurysm,” he said, reporting on the paradigm at the meeting sponsored by the American Association for Thoracic Surgery. He noted that studies from Japan of people who had died from out-of-hospital cardiac arrest found that 8% of them had a type A aortic dissection (Am J Cardiol 2016;117:1826-30).

He outlined eight “associates” of thoracic aortic aneurysm (TAA): intracranial aneurysm; bovine aortic arch; abdominal aortic aneurysm; simple renal cysts; bicuspid aortic valve; family history; positive thumb-palm test; and temporal arteritis and other autoimmune disorders.

A patient with TAA has a 10% likelihood of harboring an intracranial aneurysm (Am J Cardiol 2010;105:417-20). “It’s even more common in the descending, compared to the ascending group in examples that we’ve identified,” Dr. Elefteriades said. Particularly vulnerable are patients over age 70 and those with an intracranial aneurysm larger than 4 mm: the former has a 9% chance of harboring a TAA, the latter a 6% chance, he said.

The bovine arch had been thought to be benign, but, Dr. Elefteriades said, “We don’t think it is.”

Bovine arch refers to a group of congenital aortic arch vessels with an aberrant origin of the left common carotid artery. “We recently looked at this as a marker for thoracic aortic disease, and please note that 20% of our TAA patients have a bovine arch,” he said. “This is much higher than in the general population.”

Abdominal aortic aneurysm has long been associated with TAA, he said. “When these aneurysms are identified by ultrasound, it’s important that the thoracic aorta be checked as well,” he said.

“This is a message for internists and our vascular colleagues.”

Simple renal cysts have been found in patients with TAA at a “much higher” rate than the general population, as high as 57% of those with descending aortic aneurysms vs. 11%-13.7% of the general population, Dr. Elefteriades said (J. Am. Heart Assoc. 2016;5:e002248). Simple renal cysts are detected by abdominal CT scan. “It’s just a matter of a few more slices with the CT scan to get the entirety of the thoracic aorta evaluated,” he said.

Courtesy Dr. Elefteriades

“We encourage our radiology colleagues to do this when a renal cyst is detected.”

Bicuspid aortic valve mandates “support from our cardiac colleagues when they find one of these to let the patient know he has to be monitored lifelong for later development of this aneurysm,” Dr. Elefteriades said.

Family history of TAA has been known as a strong predictor, but genetic studies have provided clarity on the association (Arch Surg. 1999;134:361‐7). “If the proband has a thoracic aortic aneurysm, there’s 21% likelihood there’s a family member who is affected with an aneurysm somewhere in the body,” he said.

Location of aneurysms in family members is also important, Dr. Elefteriades said. “If the proband has a ascending aortic aneurysm, the kindred also have an ascending aortic aneurysm; but if the proband has a descending aneurysm, the likelihood is that the kindred will have an abdominal aortic aneurysm,” he said. “To identify silent disease, it’s very important we check siblings and children, and now, of course, we’re using whole-exome sequencing.” So far, Dr. Elefteriades has obtained whole-exome sequencing in 200 patients.

The thumb-palm test involves the patient touching the thumb to the palm; the thumb crossing the edge of the flat palm is an indicator of connective tissue disease. “It doesn’t cost anything,” Dr. Elefteriades said. “It is a very simple thing for internists to do to identify those connective tissue diseases.”

Temporal arteritis has become increasingly common in elderly women. “They have a markedly increased likelihood of having a thoracic aortic aneurysm – about 8% in some studies,’ Dr. Elefteriades said. “So we want our neurology colleagues to be aware of this and to look for thoracic aortic aneurysm.”

Dr. Elefteriades disclosed he has received consulting fees from Baxter, Covidien, Datascope, and CryoLife, and a research grant from Medtronic.

NEW YORK – Aortic aneurysm ranks as one of the top 20 causes of death in the United States. Most of these aneurysms are clinically silent until they rupture, but Yale cardiovascular surgeon John A. Elefteriades, MD, has developed a clinical paradigm that identifies eight markers that physicians can use to detect the disease before it strikes.

Dr. Elefteriades calls his paradigm “Guilt by Association.” It is based on an article he published online last year in the journal Open Heart (2015;2:e000169).

“What we need is for our colleagues in affiliated disciplines to recognize the importance of these offenders in indicating the presence of thoracic aortic aneurysm,” he said, reporting on the paradigm at the meeting sponsored by the American Association for Thoracic Surgery. He noted that studies from Japan of people who had died from out-of-hospital cardiac arrest found that 8% of them had a type A aortic dissection (Am J Cardiol 2016;117:1826-30).

He outlined eight “associates” of thoracic aortic aneurysm (TAA): intracranial aneurysm; bovine aortic arch; abdominal aortic aneurysm; simple renal cysts; bicuspid aortic valve; family history; positive thumb-palm test; and temporal arteritis and other autoimmune disorders.

A patient with TAA has a 10% likelihood of harboring an intracranial aneurysm (Am J Cardiol 2010;105:417-20). “It’s even more common in the descending, compared to the ascending group in examples that we’ve identified,” Dr. Elefteriades said. Particularly vulnerable are patients over age 70 and those with an intracranial aneurysm larger than 4 mm: the former has a 9% chance of harboring a TAA, the latter a 6% chance, he said.

The bovine arch had been thought to be benign, but, Dr. Elefteriades said, “We don’t think it is.”

Bovine arch refers to a group of congenital aortic arch vessels with an aberrant origin of the left common carotid artery. “We recently looked at this as a marker for thoracic aortic disease, and please note that 20% of our TAA patients have a bovine arch,” he said. “This is much higher than in the general population.”

Abdominal aortic aneurysm has long been associated with TAA, he said. “When these aneurysms are identified by ultrasound, it’s important that the thoracic aorta be checked as well,” he said.

“This is a message for internists and our vascular colleagues.”

Simple renal cysts have been found in patients with TAA at a “much higher” rate than the general population, as high as 57% of those with descending aortic aneurysms vs. 11%-13.7% of the general population, Dr. Elefteriades said (J. Am. Heart Assoc. 2016;5:e002248). Simple renal cysts are detected by abdominal CT scan. “It’s just a matter of a few more slices with the CT scan to get the entirety of the thoracic aorta evaluated,” he said.

Courtesy Dr. Elefteriades

“We encourage our radiology colleagues to do this when a renal cyst is detected.”

Bicuspid aortic valve mandates “support from our cardiac colleagues when they find one of these to let the patient know he has to be monitored lifelong for later development of this aneurysm,” Dr. Elefteriades said.

Family history of TAA has been known as a strong predictor, but genetic studies have provided clarity on the association (Arch Surg. 1999;134:361‐7). “If the proband has a thoracic aortic aneurysm, there’s 21% likelihood there’s a family member who is affected with an aneurysm somewhere in the body,” he said.

Location of aneurysms in family members is also important, Dr. Elefteriades said. “If the proband has a ascending aortic aneurysm, the kindred also have an ascending aortic aneurysm; but if the proband has a descending aneurysm, the likelihood is that the kindred will have an abdominal aortic aneurysm,” he said. “To identify silent disease, it’s very important we check siblings and children, and now, of course, we’re using whole-exome sequencing.” So far, Dr. Elefteriades has obtained whole-exome sequencing in 200 patients.

The thumb-palm test involves the patient touching the thumb to the palm; the thumb crossing the edge of the flat palm is an indicator of connective tissue disease. “It doesn’t cost anything,” Dr. Elefteriades said. “It is a very simple thing for internists to do to identify those connective tissue diseases.”

Temporal arteritis has become increasingly common in elderly women. “They have a markedly increased likelihood of having a thoracic aortic aneurysm – about 8% in some studies,’ Dr. Elefteriades said. “So we want our neurology colleagues to be aware of this and to look for thoracic aortic aneurysm.”

Dr. Elefteriades disclosed he has received consulting fees from Baxter, Covidien, Datascope, and CryoLife, and a research grant from Medtronic.

NEW YORK – Aortic aneurysm ranks as one of the top 20 causes of death in the United States. Most of these aneurysms are clinically silent until they rupture, but Yale cardiovascular surgeon John A. Elefteriades, MD, has developed a clinical paradigm that identifies eight markers that physicians can use to detect the disease before it strikes.

Dr. Elefteriades calls his paradigm “Guilt by Association.” It is based on an article he published online last year in the journal Open Heart (2015;2:e000169).

“What we need is for our colleagues in affiliated disciplines to recognize the importance of these offenders in indicating the presence of thoracic aortic aneurysm,” he said, reporting on the paradigm at the meeting sponsored by the American Association for Thoracic Surgery. He noted that studies from Japan of people who had died from out-of-hospital cardiac arrest found that 8% of them had a type A aortic dissection (Am J Cardiol 2016;117:1826-30).

He outlined eight “associates” of thoracic aortic aneurysm (TAA): intracranial aneurysm; bovine aortic arch; abdominal aortic aneurysm; simple renal cysts; bicuspid aortic valve; family history; positive thumb-palm test; and temporal arteritis and other autoimmune disorders.

A patient with TAA has a 10% likelihood of harboring an intracranial aneurysm (Am J Cardiol 2010;105:417-20). “It’s even more common in the descending, compared to the ascending group in examples that we’ve identified,” Dr. Elefteriades said. Particularly vulnerable are patients over age 70 and those with an intracranial aneurysm larger than 4 mm: the former has a 9% chance of harboring a TAA, the latter a 6% chance, he said.

The bovine arch had been thought to be benign, but, Dr. Elefteriades said, “We don’t think it is.”

Bovine arch refers to a group of congenital aortic arch vessels with an aberrant origin of the left common carotid artery. “We recently looked at this as a marker for thoracic aortic disease, and please note that 20% of our TAA patients have a bovine arch,” he said. “This is much higher than in the general population.”

Abdominal aortic aneurysm has long been associated with TAA, he said. “When these aneurysms are identified by ultrasound, it’s important that the thoracic aorta be checked as well,” he said.

“This is a message for internists and our vascular colleagues.”

Simple renal cysts have been found in patients with TAA at a “much higher” rate than the general population, as high as 57% of those with descending aortic aneurysms vs. 11%-13.7% of the general population, Dr. Elefteriades said (J. Am. Heart Assoc. 2016;5:e002248). Simple renal cysts are detected by abdominal CT scan. “It’s just a matter of a few more slices with the CT scan to get the entirety of the thoracic aorta evaluated,” he said.

Courtesy Dr. Elefteriades

“We encourage our radiology colleagues to do this when a renal cyst is detected.”

Bicuspid aortic valve mandates “support from our cardiac colleagues when they find one of these to let the patient know he has to be monitored lifelong for later development of this aneurysm,” Dr. Elefteriades said.

Family history of TAA has been known as a strong predictor, but genetic studies have provided clarity on the association (Arch Surg. 1999;134:361‐7). “If the proband has a thoracic aortic aneurysm, there’s 21% likelihood there’s a family member who is affected with an aneurysm somewhere in the body,” he said.

Location of aneurysms in family members is also important, Dr. Elefteriades said. “If the proband has a ascending aortic aneurysm, the kindred also have an ascending aortic aneurysm; but if the proband has a descending aneurysm, the likelihood is that the kindred will have an abdominal aortic aneurysm,” he said. “To identify silent disease, it’s very important we check siblings and children, and now, of course, we’re using whole-exome sequencing.” So far, Dr. Elefteriades has obtained whole-exome sequencing in 200 patients.

The thumb-palm test involves the patient touching the thumb to the palm; the thumb crossing the edge of the flat palm is an indicator of connective tissue disease. “It doesn’t cost anything,” Dr. Elefteriades said. “It is a very simple thing for internists to do to identify those connective tissue diseases.”

Temporal arteritis has become increasingly common in elderly women. “They have a markedly increased likelihood of having a thoracic aortic aneurysm – about 8% in some studies,’ Dr. Elefteriades said. “So we want our neurology colleagues to be aware of this and to look for thoracic aortic aneurysm.”

Dr. Elefteriades disclosed he has received consulting fees from Baxter, Covidien, Datascope, and CryoLife, and a research grant from Medtronic.

Transfusing sex-mismatched red blood cells (RBCs) was associated with an increased risk of death in people undergoing heart bypass surgery or aortic valve replacement, based on results of a retrospective single-center study of almost 10,000 transfusions in cardiac surgery patients.

Each unit of sex-mismatched red blood cells (RBCs) transfused was associated with an increased risk of death (hazard ratio, 1.083; 95% confidence interval, 1.028-1.140; P = .003). In addition, transfusing 1-2 units of non–leukocyte depleted RBCs was associated with a significant increase in the risk of death during the first year after surgery (HR, 1.426; 95% CI, 1.004-2.024; P = .047).

Transfusion of 1-2 units of leukocyte-depleted RBCs and the age of blood products was not associated with increased mortality (J Thorac Cardiovasc Surg. 2016;152:223-32.e1).

“Factors such as ABO group, Rh profile and sex of the PRBC [packed RBC] donor generally have been overlooked, as has the variation in postdonation treatment of blood,” in the outcomes of cardiac surgery patients, researchers led by Henrik Bjursten, MD, PhD, of Lund (Sweden) University, reported.

The study involved 9,907 patients at Lund University from 2002 to 2012: 7,696 had coronary artery bypass grafting (CABG); 1,216 had aortic valve replacement (AVR); and 995 concomitantly had both procedures. PRBC transfusions were given to nearly 51% of the patients. Compared with the group that did not receive PRBC transfusions, the transfused group had significantly higher rates of heart attack after surgery (1.5% vs. 0.6%), infection (0.6% vs. 0.3%), reoperation for bleeding (4.3% vs. 0.2%), 30-day death (0.7% vs. 0.2%), and overall death (25.9% vs. 12.6%).

Based on an analysis that factored in 24 different variables, transfusion of 1-2 units of non–leukocyte depleted PRBCs was associated with a HR of 1.426, but the same amount of leukocyte-depleted PRBCs did not increase risk (HR, 0.981). However, transfusion of 5-7 units of leukocyte-depleted RBCs was associated with decreased survival, as was transfusion of sex-mismatched PRBCs, associated with a HR of 1.046-1.133 per unit, Dr. Bjursten and colleagues wrote. “In this cohort, 58% of transfusions were sex mismatched, and thus we interpret the result as relatively robust and clinically relevant.”

Patients having combined CABG and AVR were more likely to have PRBC transfusions than patients who had a single procedure. Additionally, the increased death rate in the PRBC transfusion group may have been related to age and comorbidities such as diabetes, chronic obstructive pulmonary disease, and cardiac insufficiency. “Blood transfusion in part is a biomarker for advanced disease,” Dr. Bjursten and coauthors said. While patient who received PRBC transfusions may have been sicker, they did not require greater use of the ICU than patients who did not receive transfusions.

Dr. Bjursten disclosed receiving consulting fees from Boston Scientific. Coauthor Lars Algotsson, MD, PhD, disclosed receiving lecture fees from Abbott. All other authors had no financial disclosures.

Transfusing sex-mismatched red blood cells (RBCs) was associated with an increased risk of death in people undergoing heart bypass surgery or aortic valve replacement, based on results of a retrospective single-center study of almost 10,000 transfusions in cardiac surgery patients.

Each unit of sex-mismatched red blood cells (RBCs) transfused was associated with an increased risk of death (hazard ratio, 1.083; 95% confidence interval, 1.028-1.140; P = .003). In addition, transfusing 1-2 units of non–leukocyte depleted RBCs was associated with a significant increase in the risk of death during the first year after surgery (HR, 1.426; 95% CI, 1.004-2.024; P = .047).

Transfusion of 1-2 units of leukocyte-depleted RBCs and the age of blood products was not associated with increased mortality (J Thorac Cardiovasc Surg. 2016;152:223-32.e1).

“Factors such as ABO group, Rh profile and sex of the PRBC [packed RBC] donor generally have been overlooked, as has the variation in postdonation treatment of blood,” in the outcomes of cardiac surgery patients, researchers led by Henrik Bjursten, MD, PhD, of Lund (Sweden) University, reported.

The study involved 9,907 patients at Lund University from 2002 to 2012: 7,696 had coronary artery bypass grafting (CABG); 1,216 had aortic valve replacement (AVR); and 995 concomitantly had both procedures. PRBC transfusions were given to nearly 51% of the patients. Compared with the group that did not receive PRBC transfusions, the transfused group had significantly higher rates of heart attack after surgery (1.5% vs. 0.6%), infection (0.6% vs. 0.3%), reoperation for bleeding (4.3% vs. 0.2%), 30-day death (0.7% vs. 0.2%), and overall death (25.9% vs. 12.6%).

Based on an analysis that factored in 24 different variables, transfusion of 1-2 units of non–leukocyte depleted PRBCs was associated with a HR of 1.426, but the same amount of leukocyte-depleted PRBCs did not increase risk (HR, 0.981). However, transfusion of 5-7 units of leukocyte-depleted RBCs was associated with decreased survival, as was transfusion of sex-mismatched PRBCs, associated with a HR of 1.046-1.133 per unit, Dr. Bjursten and colleagues wrote. “In this cohort, 58% of transfusions were sex mismatched, and thus we interpret the result as relatively robust and clinically relevant.”

Patients having combined CABG and AVR were more likely to have PRBC transfusions than patients who had a single procedure. Additionally, the increased death rate in the PRBC transfusion group may have been related to age and comorbidities such as diabetes, chronic obstructive pulmonary disease, and cardiac insufficiency. “Blood transfusion in part is a biomarker for advanced disease,” Dr. Bjursten and coauthors said. While patient who received PRBC transfusions may have been sicker, they did not require greater use of the ICU than patients who did not receive transfusions.

Dr. Bjursten disclosed receiving consulting fees from Boston Scientific. Coauthor Lars Algotsson, MD, PhD, disclosed receiving lecture fees from Abbott. All other authors had no financial disclosures.

Transfusing sex-mismatched red blood cells (RBCs) was associated with an increased risk of death in people undergoing heart bypass surgery or aortic valve replacement, based on results of a retrospective single-center study of almost 10,000 transfusions in cardiac surgery patients.

Each unit of sex-mismatched red blood cells (RBCs) transfused was associated with an increased risk of death (hazard ratio, 1.083; 95% confidence interval, 1.028-1.140; P = .003). In addition, transfusing 1-2 units of non–leukocyte depleted RBCs was associated with a significant increase in the risk of death during the first year after surgery (HR, 1.426; 95% CI, 1.004-2.024; P = .047).

Transfusion of 1-2 units of leukocyte-depleted RBCs and the age of blood products was not associated with increased mortality (J Thorac Cardiovasc Surg. 2016;152:223-32.e1).

“Factors such as ABO group, Rh profile and sex of the PRBC [packed RBC] donor generally have been overlooked, as has the variation in postdonation treatment of blood,” in the outcomes of cardiac surgery patients, researchers led by Henrik Bjursten, MD, PhD, of Lund (Sweden) University, reported.

The study involved 9,907 patients at Lund University from 2002 to 2012: 7,696 had coronary artery bypass grafting (CABG); 1,216 had aortic valve replacement (AVR); and 995 concomitantly had both procedures. PRBC transfusions were given to nearly 51% of the patients. Compared with the group that did not receive PRBC transfusions, the transfused group had significantly higher rates of heart attack after surgery (1.5% vs. 0.6%), infection (0.6% vs. 0.3%), reoperation for bleeding (4.3% vs. 0.2%), 30-day death (0.7% vs. 0.2%), and overall death (25.9% vs. 12.6%).

Based on an analysis that factored in 24 different variables, transfusion of 1-2 units of non–leukocyte depleted PRBCs was associated with a HR of 1.426, but the same amount of leukocyte-depleted PRBCs did not increase risk (HR, 0.981). However, transfusion of 5-7 units of leukocyte-depleted RBCs was associated with decreased survival, as was transfusion of sex-mismatched PRBCs, associated with a HR of 1.046-1.133 per unit, Dr. Bjursten and colleagues wrote. “In this cohort, 58% of transfusions were sex mismatched, and thus we interpret the result as relatively robust and clinically relevant.”

Patients having combined CABG and AVR were more likely to have PRBC transfusions than patients who had a single procedure. Additionally, the increased death rate in the PRBC transfusion group may have been related to age and comorbidities such as diabetes, chronic obstructive pulmonary disease, and cardiac insufficiency. “Blood transfusion in part is a biomarker for advanced disease,” Dr. Bjursten and coauthors said. While patient who received PRBC transfusions may have been sicker, they did not require greater use of the ICU than patients who did not receive transfusions.

Dr. Bjursten disclosed receiving consulting fees from Boston Scientific. Coauthor Lars Algotsson, MD, PhD, disclosed receiving lecture fees from Abbott. All other authors had no financial disclosures.

NEW ORLEANS – Quality of life measures are sorely lacking for patients with type 1 diabetes, but researchers are attempting to identify measures of patient well-being that go beyond the hemoglobin A_1c (HbA_1c) level.

At a symposium at the annual scientific sessions of the American Diabetes Association, moderator Kimberly A. Driscoll, PhD, of the University of Colorado, said that “measuring quality of life [should become] a standard part of the routine diabetes clinic visit, just like taking blood pressure.” Parents, partners, and caregivers also need to be involved in deciding what quality of life measures matter, as they are the patients’ sources of support.

Marisa E. Hilliard, PhD, reported on her research team’s efforts to glean from questionnaires the measures that would matter to those with type 1 diabetes and their caregivers. The goal is to create a tool to measure diabetes-related quality of life.

“We want to be able to track quality of life over time and understand how it’s different for different people, and there is not great research on that data,” said Dr. Hilliard of Baylor College of Medicine/Texas Children’s Hospital, Houston.

Lawrence Fisher, PhD, concurred that a quality of life research gap exists for those with type 1 diabetes. A PubMed search indicates that 1,273 papers were published in 2015 with the key words “diabetes” and “quality of life,” yet few of these papers had designated quality of life as a primary outcome. In type 1 diabetes, quality of life “is comprised of one gigantic bucket into which we have thrown all kinds of things, and it’s mired by dozens of different kinds of measures that are all called ‘quality of life’ but define and measure it in very different ways,” said Dr. Fisher of the Behavioral Diabetes Research Group at the University of California, San Francisco.

Patient management in diabetes is a three-legged stool comprised of equal components of glycemic control, behavioral change, and quality of life. Patients are living longer and have healthier lives, but “I don’t think we’re doing as good a job with the happy” aspect of patients’ lives, he said “We spend far too much time treating glucose numbers and not enough time treating people.”

Without measuring quality of life, “you never evaluate the actual cost to individuals of achieving a gain in improved HbA_1c or improved behavioral change.”

“I’m told that today, at this point, there are between 15 and 20 diabetes-specific quality of life scales,” he said. “It’s a real hodgepodge. … and one shouldn’t “just go in and pull the measure off the shelf because it has ‘quality of life’ in the title.” The measure must also take into account factors such as patient age, gender, and ethnicity.

Dr. Hilliard and her team are trying to address the “major lack of developmentally tailored measurement instruments. When you have diabetes, you have it for life, and the issues relevant to your quality of life change from age 8 to 18 to 40 and so on.”

Based on interviews with 81 people with type 1 diabetes and their caregivers, the research team developed 14 different measures specifically designed for seven different age bands of people with diabetes – from age 8 years and younger through age 60 years and older. Each age band, with the exception of age 8 years and younger, involves self-reporting by the patient and either the parent, partner, or caregiver. Only the parent self-reports in the youngest age band.

To validate the measures, the researchers plan to enroll 3,600 participants at six sites from the Type 1 Diabetes Exchange and hope to have results in about 18 months. “Our goal is to get the questionnaire to less than 30 items so it takes less than 5 minutes to complete, and to develop a scoring system,” Dr. Hilliard said.

Besides patient care, the measures could be used for clinical trials across the lifespan of people with type 1 diabetes and quality improvement initiatives, she said. Once established, an expert committee would review the measures every 5 years and update them as needed.

Dr. Fisher disclosed he is a consultant to Abbott, Eli Lilly and Company, and Roche Diagnostics.

Dr. Hilliard had no financial disclosures. The Leona M. and Harry B. Helmsley Charitable Trust and the National Institutes of Diabetes and Digestive and Kidney Disease have provided funding for her study.

NEW ORLEANS – Quality of life measures are sorely lacking for patients with type 1 diabetes, but researchers are attempting to identify measures of patient well-being that go beyond the hemoglobin A_1c (HbA_1c) level.

At a symposium at the annual scientific sessions of the American Diabetes Association, moderator Kimberly A. Driscoll, PhD, of the University of Colorado, said that “measuring quality of life [should become] a standard part of the routine diabetes clinic visit, just like taking blood pressure.” Parents, partners, and caregivers also need to be involved in deciding what quality of life measures matter, as they are the patients’ sources of support.

Marisa E. Hilliard, PhD, reported on her research team’s efforts to glean from questionnaires the measures that would matter to those with type 1 diabetes and their caregivers. The goal is to create a tool to measure diabetes-related quality of life.

“We want to be able to track quality of life over time and understand how it’s different for different people, and there is not great research on that data,” said Dr. Hilliard of Baylor College of Medicine/Texas Children’s Hospital, Houston.

Lawrence Fisher, PhD, concurred that a quality of life research gap exists for those with type 1 diabetes. A PubMed search indicates that 1,273 papers were published in 2015 with the key words “diabetes” and “quality of life,” yet few of these papers had designated quality of life as a primary outcome. In type 1 diabetes, quality of life “is comprised of one gigantic bucket into which we have thrown all kinds of things, and it’s mired by dozens of different kinds of measures that are all called ‘quality of life’ but define and measure it in very different ways,” said Dr. Fisher of the Behavioral Diabetes Research Group at the University of California, San Francisco.

Patient management in diabetes is a three-legged stool comprised of equal components of glycemic control, behavioral change, and quality of life. Patients are living longer and have healthier lives, but “I don’t think we’re doing as good a job with the happy” aspect of patients’ lives, he said “We spend far too much time treating glucose numbers and not enough time treating people.”

Without measuring quality of life, “you never evaluate the actual cost to individuals of achieving a gain in improved HbA_1c or improved behavioral change.”

“I’m told that today, at this point, there are between 15 and 20 diabetes-specific quality of life scales,” he said. “It’s a real hodgepodge. … and one shouldn’t “just go in and pull the measure off the shelf because it has ‘quality of life’ in the title.” The measure must also take into account factors such as patient age, gender, and ethnicity.

Dr. Hilliard and her team are trying to address the “major lack of developmentally tailored measurement instruments. When you have diabetes, you have it for life, and the issues relevant to your quality of life change from age 8 to 18 to 40 and so on.”

Based on interviews with 81 people with type 1 diabetes and their caregivers, the research team developed 14 different measures specifically designed for seven different age bands of people with diabetes – from age 8 years and younger through age 60 years and older. Each age band, with the exception of age 8 years and younger, involves self-reporting by the patient and either the parent, partner, or caregiver. Only the parent self-reports in the youngest age band.

To validate the measures, the researchers plan to enroll 3,600 participants at six sites from the Type 1 Diabetes Exchange and hope to have results in about 18 months. “Our goal is to get the questionnaire to less than 30 items so it takes less than 5 minutes to complete, and to develop a scoring system,” Dr. Hilliard said.

Besides patient care, the measures could be used for clinical trials across the lifespan of people with type 1 diabetes and quality improvement initiatives, she said. Once established, an expert committee would review the measures every 5 years and update them as needed.

Dr. Fisher disclosed he is a consultant to Abbott, Eli Lilly and Company, and Roche Diagnostics.

Dr. Hilliard had no financial disclosures. The Leona M. and Harry B. Helmsley Charitable Trust and the National Institutes of Diabetes and Digestive and Kidney Disease have provided funding for her study.

NEW ORLEANS – Quality of life measures are sorely lacking for patients with type 1 diabetes, but researchers are attempting to identify measures of patient well-being that go beyond the hemoglobin A_1c (HbA_1c) level.

At a symposium at the annual scientific sessions of the American Diabetes Association, moderator Kimberly A. Driscoll, PhD, of the University of Colorado, said that “measuring quality of life [should become] a standard part of the routine diabetes clinic visit, just like taking blood pressure.” Parents, partners, and caregivers also need to be involved in deciding what quality of life measures matter, as they are the patients’ sources of support.

Marisa E. Hilliard, PhD, reported on her research team’s efforts to glean from questionnaires the measures that would matter to those with type 1 diabetes and their caregivers. The goal is to create a tool to measure diabetes-related quality of life.

“We want to be able to track quality of life over time and understand how it’s different for different people, and there is not great research on that data,” said Dr. Hilliard of Baylor College of Medicine/Texas Children’s Hospital, Houston.

Lawrence Fisher, PhD, concurred that a quality of life research gap exists for those with type 1 diabetes. A PubMed search indicates that 1,273 papers were published in 2015 with the key words “diabetes” and “quality of life,” yet few of these papers had designated quality of life as a primary outcome. In type 1 diabetes, quality of life “is comprised of one gigantic bucket into which we have thrown all kinds of things, and it’s mired by dozens of different kinds of measures that are all called ‘quality of life’ but define and measure it in very different ways,” said Dr. Fisher of the Behavioral Diabetes Research Group at the University of California, San Francisco.

Patient management in diabetes is a three-legged stool comprised of equal components of glycemic control, behavioral change, and quality of life. Patients are living longer and have healthier lives, but “I don’t think we’re doing as good a job with the happy” aspect of patients’ lives, he said “We spend far too much time treating glucose numbers and not enough time treating people.”

Without measuring quality of life, “you never evaluate the actual cost to individuals of achieving a gain in improved HbA_1c or improved behavioral change.”

“I’m told that today, at this point, there are between 15 and 20 diabetes-specific quality of life scales,” he said. “It’s a real hodgepodge. … and one shouldn’t “just go in and pull the measure off the shelf because it has ‘quality of life’ in the title.” The measure must also take into account factors such as patient age, gender, and ethnicity.

Dr. Hilliard and her team are trying to address the “major lack of developmentally tailored measurement instruments. When you have diabetes, you have it for life, and the issues relevant to your quality of life change from age 8 to 18 to 40 and so on.”

Based on interviews with 81 people with type 1 diabetes and their caregivers, the research team developed 14 different measures specifically designed for seven different age bands of people with diabetes – from age 8 years and younger through age 60 years and older. Each age band, with the exception of age 8 years and younger, involves self-reporting by the patient and either the parent, partner, or caregiver. Only the parent self-reports in the youngest age band.

To validate the measures, the researchers plan to enroll 3,600 participants at six sites from the Type 1 Diabetes Exchange and hope to have results in about 18 months. “Our goal is to get the questionnaire to less than 30 items so it takes less than 5 minutes to complete, and to develop a scoring system,” Dr. Hilliard said.

Besides patient care, the measures could be used for clinical trials across the lifespan of people with type 1 diabetes and quality improvement initiatives, she said. Once established, an expert committee would review the measures every 5 years and update them as needed.

Dr. Fisher disclosed he is a consultant to Abbott, Eli Lilly and Company, and Roche Diagnostics.

Dr. Hilliard had no financial disclosures. The Leona M. and Harry B. Helmsley Charitable Trust and the National Institutes of Diabetes and Digestive and Kidney Disease have provided funding for her study.

NEW ORLEANS – An investigational endoscopic procedure that aims to disrupt how the gut absorbs nutrients according to principles of gastric bypass surgery achieved reductions in hemoglobin A_1c levels and improvement in other key metabolic parameters in people with type 2 diabetes participating in a single-center investigational study in Santiago, Chile.

The procedure, called duodenal mucosal resurfacing (DMR), uses a balloon catheter to thermally ablate about 10 cm of the duodenal mucosa, Alan Cherrington, Ph.D., of Vanderbilt University, Nashville, Tenn., reported at the annual scientific sessions of the American Diabetes Association.

“A lot of the gastric bypass surgeries have been very effective in not only creating weight loss but in improving glucose tolerance,” Dr. Cherrington said. “The problem is, of course, they are very invasive and difficult to do, so the hope here was to try and develop a technique which in fact would be simpler but perhaps achieve some of the same effects.”

The mucosa in people with type 2 diabetes has been known to be thickened, and the endocrine cells discommuted and morphed, Dr. Cherrington explained. “So the question was, is there a way to do something about that?” The procedure, he said, was “well tolerated” and achieved significant reduction of HbA_1c after 3 months.

An international group of bariatric experts participated in the trial report. Dr. Cherrington said the procedure involves inserting a balloon-tipped catheter through the esophagus and stomach and into the duodenum, and then seating the balloon snugly in the mucosa at the ampulla of Vater. “You need a snug fit between the balloon and the mucosa,” Dr. Cherrington said.

Once the catheter is in place, it is filled with saline that inflates the balloon to fill the space. At that point, heated saline is run through the catheter for 10 seconds, creating a circumferential ablation of 300-500 mcm. When that step is completed, the balloon is moved down approximately 2 cm and the process repeated until the full 10 cm of the duodenal length from the ampulla of Vater to the ligament of Treitz is ablated.

A trained endoscopist performed the procedure with the patients under anesthesia, Dr. Cherrington said. The average HbA_1c was 9.6% at baseline, and the 39 patients were on one or more antidiabetic agents. The average fasting plasma glucose was 187 mg/dL at baseline. Average age was 54 years, and two-thirds of patients were male.

“It was not a mechanistic study,” Dr. Cherrington said. “It was a study purely to see: Can we do this? Can it be done safely? And would there be any efficacy at all?” The patients actually received DMR of two lengths: a short-segment ablation of 3.4 cm (n = 11); and a long-segment approach of 9.3 cm (n = 28).

“Patients had no difficulty tolerating an oral diet within days of the procedure,” Dr. Cherrington said. He described the adverse events as “mild,” mostly occurring immediately after the procedure. They typically involved tenderness due to anesthesia intubation or the endoscopic procedure itself, resolving in 3 days. Three patients had stenosis “very early while the device was still in its iterative development,” Dr. Cherrington said. But since the device was modified, the episodes of stenosis were mild and “resolved easily” with dilation.

The 9.3-cm ablation achieved better outcomes than did the 3.4-cm ablation, Dr. Cherrington said. Those in the long-segment group with baseline HbA_1c as high as 11% averaged 7.5% 3 months post ablation; those with HbA_1c around 9% before ablation averaged “just below 7%” afterward, he said. The patients showed some “waning effect” in HbA_1c after 6 months.

A cohort of patients who continued their medications achieved even better results. “They came to an HbA_1c of 6.5% and drifted up minimally at 6 months,” Dr. Cherrington said. “Part of the drift upward of the others was a function that they began to come off their medications.” Other reported metabolic parameters also showed improvement.

The next step, Dr. Cherrington said, is to compile 6-month results in an ongoing trial called Revita-1 in Chile and at five centers in Europe; after that, the goal is to conduct a multicenter phase II trial, Revita-2 that will include U.S. centers. “Clearly there are many, many questions that remain to be answered, and further examination of the efficacy, of the safety, of the clinical utility, and not the least of which is what is the mechanism by which this comes about, is essential,” Dr. Cherrington said.

Dr. John M. Miles of the University of Kansas Hospital in Kansas City gave a preview of some of those questions: “I would love to know whether metformin pharmacokinetics are altered by this procedure.” Dr. Miles asked for an explanation of the initial weight loss in study patients. “I would love to see self-reported calorie counts with these people,” he said.

Dr. Cherrington said the ensuing trials would aim to answer the first question, but that no information on calorie counts was available. The patients experienced an immediate weight loss after DMR but then some rebound effect after that, he said.

Dr. Cherrington disclosed relationships with Biocon, Fractyl, Merck, Metavention, NuSirt Biopharma, Sensulin, Zafgen, Eli Lilly, Silver Lake, Islet Sciences, Novo Nordisk, Profil Institute for Clinical Research, Thermalin Diabetes, Thetis Pharmaceuticals, vTv Therapeutics, ViaCyte, and Viking.

NEW ORLEANS – An investigational endoscopic procedure that aims to disrupt how the gut absorbs nutrients according to principles of gastric bypass surgery achieved reductions in hemoglobin A_1c levels and improvement in other key metabolic parameters in people with type 2 diabetes participating in a single-center investigational study in Santiago, Chile.

The procedure, called duodenal mucosal resurfacing (DMR), uses a balloon catheter to thermally ablate about 10 cm of the duodenal mucosa, Alan Cherrington, Ph.D., of Vanderbilt University, Nashville, Tenn., reported at the annual scientific sessions of the American Diabetes Association.

“A lot of the gastric bypass surgeries have been very effective in not only creating weight loss but in improving glucose tolerance,” Dr. Cherrington said. “The problem is, of course, they are very invasive and difficult to do, so the hope here was to try and develop a technique which in fact would be simpler but perhaps achieve some of the same effects.”

The mucosa in people with type 2 diabetes has been known to be thickened, and the endocrine cells discommuted and morphed, Dr. Cherrington explained. “So the question was, is there a way to do something about that?” The procedure, he said, was “well tolerated” and achieved significant reduction of HbA_1c after 3 months.

An international group of bariatric experts participated in the trial report. Dr. Cherrington said the procedure involves inserting a balloon-tipped catheter through the esophagus and stomach and into the duodenum, and then seating the balloon snugly in the mucosa at the ampulla of Vater. “You need a snug fit between the balloon and the mucosa,” Dr. Cherrington said.

Once the catheter is in place, it is filled with saline that inflates the balloon to fill the space. At that point, heated saline is run through the catheter for 10 seconds, creating a circumferential ablation of 300-500 mcm. When that step is completed, the balloon is moved down approximately 2 cm and the process repeated until the full 10 cm of the duodenal length from the ampulla of Vater to the ligament of Treitz is ablated.

A trained endoscopist performed the procedure with the patients under anesthesia, Dr. Cherrington said. The average HbA_1c was 9.6% at baseline, and the 39 patients were on one or more antidiabetic agents. The average fasting plasma glucose was 187 mg/dL at baseline. Average age was 54 years, and two-thirds of patients were male.

“It was not a mechanistic study,” Dr. Cherrington said. “It was a study purely to see: Can we do this? Can it be done safely? And would there be any efficacy at all?” The patients actually received DMR of two lengths: a short-segment ablation of 3.4 cm (n = 11); and a long-segment approach of 9.3 cm (n = 28).

“Patients had no difficulty tolerating an oral diet within days of the procedure,” Dr. Cherrington said. He described the adverse events as “mild,” mostly occurring immediately after the procedure. They typically involved tenderness due to anesthesia intubation or the endoscopic procedure itself, resolving in 3 days. Three patients had stenosis “very early while the device was still in its iterative development,” Dr. Cherrington said. But since the device was modified, the episodes of stenosis were mild and “resolved easily” with dilation.

The 9.3-cm ablation achieved better outcomes than did the 3.4-cm ablation, Dr. Cherrington said. Those in the long-segment group with baseline HbA_1c as high as 11% averaged 7.5% 3 months post ablation; those with HbA_1c around 9% before ablation averaged “just below 7%” afterward, he said. The patients showed some “waning effect” in HbA_1c after 6 months.

A cohort of patients who continued their medications achieved even better results. “They came to an HbA_1c of 6.5% and drifted up minimally at 6 months,” Dr. Cherrington said. “Part of the drift upward of the others was a function that they began to come off their medications.” Other reported metabolic parameters also showed improvement.

The next step, Dr. Cherrington said, is to compile 6-month results in an ongoing trial called Revita-1 in Chile and at five centers in Europe; after that, the goal is to conduct a multicenter phase II trial, Revita-2 that will include U.S. centers. “Clearly there are many, many questions that remain to be answered, and further examination of the efficacy, of the safety, of the clinical utility, and not the least of which is what is the mechanism by which this comes about, is essential,” Dr. Cherrington said.

Dr. John M. Miles of the University of Kansas Hospital in Kansas City gave a preview of some of those questions: “I would love to know whether metformin pharmacokinetics are altered by this procedure.” Dr. Miles asked for an explanation of the initial weight loss in study patients. “I would love to see self-reported calorie counts with these people,” he said.

Dr. Cherrington said the ensuing trials would aim to answer the first question, but that no information on calorie counts was available. The patients experienced an immediate weight loss after DMR but then some rebound effect after that, he said.

Dr. Cherrington disclosed relationships with Biocon, Fractyl, Merck, Metavention, NuSirt Biopharma, Sensulin, Zafgen, Eli Lilly, Silver Lake, Islet Sciences, Novo Nordisk, Profil Institute for Clinical Research, Thermalin Diabetes, Thetis Pharmaceuticals, vTv Therapeutics, ViaCyte, and Viking.

NEW ORLEANS – An investigational endoscopic procedure that aims to disrupt how the gut absorbs nutrients according to principles of gastric bypass surgery achieved reductions in hemoglobin A_1c levels and improvement in other key metabolic parameters in people with type 2 diabetes participating in a single-center investigational study in Santiago, Chile.

The procedure, called duodenal mucosal resurfacing (DMR), uses a balloon catheter to thermally ablate about 10 cm of the duodenal mucosa, Alan Cherrington, Ph.D., of Vanderbilt University, Nashville, Tenn., reported at the annual scientific sessions of the American Diabetes Association.

“A lot of the gastric bypass surgeries have been very effective in not only creating weight loss but in improving glucose tolerance,” Dr. Cherrington said. “The problem is, of course, they are very invasive and difficult to do, so the hope here was to try and develop a technique which in fact would be simpler but perhaps achieve some of the same effects.”

The mucosa in people with type 2 diabetes has been known to be thickened, and the endocrine cells discommuted and morphed, Dr. Cherrington explained. “So the question was, is there a way to do something about that?” The procedure, he said, was “well tolerated” and achieved significant reduction of HbA_1c after 3 months.

An international group of bariatric experts participated in the trial report. Dr. Cherrington said the procedure involves inserting a balloon-tipped catheter through the esophagus and stomach and into the duodenum, and then seating the balloon snugly in the mucosa at the ampulla of Vater. “You need a snug fit between the balloon and the mucosa,” Dr. Cherrington said.

Once the catheter is in place, it is filled with saline that inflates the balloon to fill the space. At that point, heated saline is run through the catheter for 10 seconds, creating a circumferential ablation of 300-500 mcm. When that step is completed, the balloon is moved down approximately 2 cm and the process repeated until the full 10 cm of the duodenal length from the ampulla of Vater to the ligament of Treitz is ablated.

A trained endoscopist performed the procedure with the patients under anesthesia, Dr. Cherrington said. The average HbA_1c was 9.6% at baseline, and the 39 patients were on one or more antidiabetic agents. The average fasting plasma glucose was 187 mg/dL at baseline. Average age was 54 years, and two-thirds of patients were male.

“It was not a mechanistic study,” Dr. Cherrington said. “It was a study purely to see: Can we do this? Can it be done safely? And would there be any efficacy at all?” The patients actually received DMR of two lengths: a short-segment ablation of 3.4 cm (n = 11); and a long-segment approach of 9.3 cm (n = 28).

“Patients had no difficulty tolerating an oral diet within days of the procedure,” Dr. Cherrington said. He described the adverse events as “mild,” mostly occurring immediately after the procedure. They typically involved tenderness due to anesthesia intubation or the endoscopic procedure itself, resolving in 3 days. Three patients had stenosis “very early while the device was still in its iterative development,” Dr. Cherrington said. But since the device was modified, the episodes of stenosis were mild and “resolved easily” with dilation.

The 9.3-cm ablation achieved better outcomes than did the 3.4-cm ablation, Dr. Cherrington said. Those in the long-segment group with baseline HbA_1c as high as 11% averaged 7.5% 3 months post ablation; those with HbA_1c around 9% before ablation averaged “just below 7%” afterward, he said. The patients showed some “waning effect” in HbA_1c after 6 months.

A cohort of patients who continued their medications achieved even better results. “They came to an HbA_1c of 6.5% and drifted up minimally at 6 months,” Dr. Cherrington said. “Part of the drift upward of the others was a function that they began to come off their medications.” Other reported metabolic parameters also showed improvement.

The next step, Dr. Cherrington said, is to compile 6-month results in an ongoing trial called Revita-1 in Chile and at five centers in Europe; after that, the goal is to conduct a multicenter phase II trial, Revita-2 that will include U.S. centers. “Clearly there are many, many questions that remain to be answered, and further examination of the efficacy, of the safety, of the clinical utility, and not the least of which is what is the mechanism by which this comes about, is essential,” Dr. Cherrington said.

Dr. John M. Miles of the University of Kansas Hospital in Kansas City gave a preview of some of those questions: “I would love to know whether metformin pharmacokinetics are altered by this procedure.” Dr. Miles asked for an explanation of the initial weight loss in study patients. “I would love to see self-reported calorie counts with these people,” he said.

Dr. Cherrington said the ensuing trials would aim to answer the first question, but that no information on calorie counts was available. The patients experienced an immediate weight loss after DMR but then some rebound effect after that, he said.

Dr. Cherrington disclosed relationships with Biocon, Fractyl, Merck, Metavention, NuSirt Biopharma, Sensulin, Zafgen, Eli Lilly, Silver Lake, Islet Sciences, Novo Nordisk, Profil Institute for Clinical Research, Thermalin Diabetes, Thetis Pharmaceuticals, vTv Therapeutics, ViaCyte, and Viking.

NEW ORLEANS – When used as an add-on therapy to metformin in patients with type 2 diabetes mellitus, empagliflozin has sustained safety and efficacy in reducing in hemoglobin A_1c (HbA_1c) and other key metabolic measures for up to 4 years, according to results of the EMPA-REG H2H-SU trial presented at the annual scientific sessions of the American Diabetes Association.

The latest results of the double-blind, phase III trial extended out to 4 years the previously published 2-year results (Lancet Diabetes Endocrinol. 2014;2:691-700) in comparing empagliflozin, a sodium glucose cotransporter inhibitor, 25 mg daily, and the sulfonylurea glimepiride, 1-4 mg daily, as add-on therapy to metformin. “As previously reported, after 2 years there was a modest difference in HbA_1c between empagliflozin and glimepiride,” said Dr. Afshin Salsali, reporting for the trial group. “This difference continued for the remainder of the study, although there was a slight rebound in each group,” according to Dr. Salsali, executive director of global clinical development at Boehringer Ingelheim, Ridgefield, Conn.

The 4-year results involved more than 73% of the 1,545 patients who participated in the 2-year study, Dr. Salsali said. The majority of patients were white, with average HbA_1c levels of 7.92% and weight of 82.5 kg at the outset of the 2-year study. After 4 years, average HbA_1c levels declined 0.08% in those on glimepiride vs. 0.26% for empagliflozin, Dr. Salsali said, achieving the primary study endpoint of noninferiority to glimepiride. However, he noted that rates of hypoglycemia varied dramatically between the two therapies. “This was achieved at the rate of much lower hypoglycemia on empagliflozin, compared with glimepiride, 3% vs. 25% (P less than .001),” he said.

Dr. Salsali pointed out that patients in the empagliflozin group were less likely to need rescue therapy, with an odds ratio of 0.56 (P less than.001), and a much later need for intervention. The advantage empagliflozin showed in both weight loss and blood pressure reduction in the 2-year study also held up for 4 years, Dr. Salsali said. “The pattern of blood pressure reduction achieved at initiation in the first few weeks after using empagliflozin more or less remained at the same level throughout this study,” he said.

One of most important messages from the study, Dr. Salsali said, is the impact empagliflozin had on the estimated glomerular filtration rate (eGFR). “Previously in the pivotal diabetes trial that we had, we showed a reduction in eGFR with a slight rebound, but we didn’t have enough time to see the full picture,” he said. “Now we have the luxury of looking into the full eGFR change over time up to 4 years. After the initial reduction in eGFR, there is a gradual increase and return of eGFR to the baseline level which remained stable for the duration of this study.” However, the glimepiride arm showed the “expected” average rate of eGFR reduction of 2 mL/min per year for type 2 diabetes, he said.

The reporting of adverse events was about the same between both groups, but serious adverse events were slightly higher among those on empagliflozin: 7.36/100 patient years vs. 7.06/100 patient years on glimepiride. The former had higher rates of urinary tract infections (6.96 vs. 5.82 per 100 patient-years) and volume depletion (0.82 vs. 0.63 per 100 patient years), but rates of bone fractures were almost identical (4.1% vs. 4.2%). There was no reported diabetic ketoacidosis in either group.

“Empagliflozin 25 mg after 208 weeks of treatment as an add-on to metformin led to modest numerical advantage in mean HbA_1c change from baseline and clinically relevant reduction in weight, systolic blood pressure, and diastolic blood pressure,” Dr. Salsali said. “The difference in changes in HbA_1c between empagliflozin and glimepiride were small, but empagliflozin was associated with a significant lower risk of hypoglycemia and significantly fewer patients required rescue therapy.”

Besides Dr. Salsali’s disclosure, coauthors disclosed relationships with Novo Nordisk, Medtronic, and the Steno Diabetes Center. Three other coauthors were employees of Boehringer Ingelheim.

NEW ORLEANS – When used as an add-on therapy to metformin in patients with type 2 diabetes mellitus, empagliflozin has sustained safety and efficacy in reducing in hemoglobin A_1c (HbA_1c) and other key metabolic measures for up to 4 years, according to results of the EMPA-REG H2H-SU trial presented at the annual scientific sessions of the American Diabetes Association.

The latest results of the double-blind, phase III trial extended out to 4 years the previously published 2-year results (Lancet Diabetes Endocrinol. 2014;2:691-700) in comparing empagliflozin, a sodium glucose cotransporter inhibitor, 25 mg daily, and the sulfonylurea glimepiride, 1-4 mg daily, as add-on therapy to metformin. “As previously reported, after 2 years there was a modest difference in HbA_1c between empagliflozin and glimepiride,” said Dr. Afshin Salsali, reporting for the trial group. “This difference continued for the remainder of the study, although there was a slight rebound in each group,” according to Dr. Salsali, executive director of global clinical development at Boehringer Ingelheim, Ridgefield, Conn.

The 4-year results involved more than 73% of the 1,545 patients who participated in the 2-year study, Dr. Salsali said. The majority of patients were white, with average HbA_1c levels of 7.92% and weight of 82.5 kg at the outset of the 2-year study. After 4 years, average HbA_1c levels declined 0.08% in those on glimepiride vs. 0.26% for empagliflozin, Dr. Salsali said, achieving the primary study endpoint of noninferiority to glimepiride. However, he noted that rates of hypoglycemia varied dramatically between the two therapies. “This was achieved at the rate of much lower hypoglycemia on empagliflozin, compared with glimepiride, 3% vs. 25% (P less than .001),” he said.

Dr. Salsali pointed out that patients in the empagliflozin group were less likely to need rescue therapy, with an odds ratio of 0.56 (P less than.001), and a much later need for intervention. The advantage empagliflozin showed in both weight loss and blood pressure reduction in the 2-year study also held up for 4 years, Dr. Salsali said. “The pattern of blood pressure reduction achieved at initiation in the first few weeks after using empagliflozin more or less remained at the same level throughout this study,” he said.

One of most important messages from the study, Dr. Salsali said, is the impact empagliflozin had on the estimated glomerular filtration rate (eGFR). “Previously in the pivotal diabetes trial that we had, we showed a reduction in eGFR with a slight rebound, but we didn’t have enough time to see the full picture,” he said. “Now we have the luxury of looking into the full eGFR change over time up to 4 years. After the initial reduction in eGFR, there is a gradual increase and return of eGFR to the baseline level which remained stable for the duration of this study.” However, the glimepiride arm showed the “expected” average rate of eGFR reduction of 2 mL/min per year for type 2 diabetes, he said.

The reporting of adverse events was about the same between both groups, but serious adverse events were slightly higher among those on empagliflozin: 7.36/100 patient years vs. 7.06/100 patient years on glimepiride. The former had higher rates of urinary tract infections (6.96 vs. 5.82 per 100 patient-years) and volume depletion (0.82 vs. 0.63 per 100 patient years), but rates of bone fractures were almost identical (4.1% vs. 4.2%). There was no reported diabetic ketoacidosis in either group.

“Empagliflozin 25 mg after 208 weeks of treatment as an add-on to metformin led to modest numerical advantage in mean HbA_1c change from baseline and clinically relevant reduction in weight, systolic blood pressure, and diastolic blood pressure,” Dr. Salsali said. “The difference in changes in HbA_1c between empagliflozin and glimepiride were small, but empagliflozin was associated with a significant lower risk of hypoglycemia and significantly fewer patients required rescue therapy.”

Besides Dr. Salsali’s disclosure, coauthors disclosed relationships with Novo Nordisk, Medtronic, and the Steno Diabetes Center. Three other coauthors were employees of Boehringer Ingelheim.

NEW ORLEANS – When used as an add-on therapy to metformin in patients with type 2 diabetes mellitus, empagliflozin has sustained safety and efficacy in reducing in hemoglobin A_1c (HbA_1c) and other key metabolic measures for up to 4 years, according to results of the EMPA-REG H2H-SU trial presented at the annual scientific sessions of the American Diabetes Association.

The latest results of the double-blind, phase III trial extended out to 4 years the previously published 2-year results (Lancet Diabetes Endocrinol. 2014;2:691-700) in comparing empagliflozin, a sodium glucose cotransporter inhibitor, 25 mg daily, and the sulfonylurea glimepiride, 1-4 mg daily, as add-on therapy to metformin. “As previously reported, after 2 years there was a modest difference in HbA_1c between empagliflozin and glimepiride,” said Dr. Afshin Salsali, reporting for the trial group. “This difference continued for the remainder of the study, although there was a slight rebound in each group,” according to Dr. Salsali, executive director of global clinical development at Boehringer Ingelheim, Ridgefield, Conn.

The 4-year results involved more than 73% of the 1,545 patients who participated in the 2-year study, Dr. Salsali said. The majority of patients were white, with average HbA_1c levels of 7.92% and weight of 82.5 kg at the outset of the 2-year study. After 4 years, average HbA_1c levels declined 0.08% in those on glimepiride vs. 0.26% for empagliflozin, Dr. Salsali said, achieving the primary study endpoint of noninferiority to glimepiride. However, he noted that rates of hypoglycemia varied dramatically between the two therapies. “This was achieved at the rate of much lower hypoglycemia on empagliflozin, compared with glimepiride, 3% vs. 25% (P less than .001),” he said.

Dr. Salsali pointed out that patients in the empagliflozin group were less likely to need rescue therapy, with an odds ratio of 0.56 (P less than.001), and a much later need for intervention. The advantage empagliflozin showed in both weight loss and blood pressure reduction in the 2-year study also held up for 4 years, Dr. Salsali said. “The pattern of blood pressure reduction achieved at initiation in the first few weeks after using empagliflozin more or less remained at the same level throughout this study,” he said.

One of most important messages from the study, Dr. Salsali said, is the impact empagliflozin had on the estimated glomerular filtration rate (eGFR). “Previously in the pivotal diabetes trial that we had, we showed a reduction in eGFR with a slight rebound, but we didn’t have enough time to see the full picture,” he said. “Now we have the luxury of looking into the full eGFR change over time up to 4 years. After the initial reduction in eGFR, there is a gradual increase and return of eGFR to the baseline level which remained stable for the duration of this study.” However, the glimepiride arm showed the “expected” average rate of eGFR reduction of 2 mL/min per year for type 2 diabetes, he said.

The reporting of adverse events was about the same between both groups, but serious adverse events were slightly higher among those on empagliflozin: 7.36/100 patient years vs. 7.06/100 patient years on glimepiride. The former had higher rates of urinary tract infections (6.96 vs. 5.82 per 100 patient-years) and volume depletion (0.82 vs. 0.63 per 100 patient years), but rates of bone fractures were almost identical (4.1% vs. 4.2%). There was no reported diabetic ketoacidosis in either group.

“Empagliflozin 25 mg after 208 weeks of treatment as an add-on to metformin led to modest numerical advantage in mean HbA_1c change from baseline and clinically relevant reduction in weight, systolic blood pressure, and diastolic blood pressure,” Dr. Salsali said. “The difference in changes in HbA_1c between empagliflozin and glimepiride were small, but empagliflozin was associated with a significant lower risk of hypoglycemia and significantly fewer patients required rescue therapy.”

Besides Dr. Salsali’s disclosure, coauthors disclosed relationships with Novo Nordisk, Medtronic, and the Steno Diabetes Center. Three other coauthors were employees of Boehringer Ingelheim.

NEW ORLEANS – If the yardstick for measuring the cost-effectiveness of an operation or a medical treatment is that it costs less than $50,000 for each quality-adjusted life-year gained, then weight-loss surgery as a treatment for type 2 diabetes is cost-effective.

However, more long-term follow-up is needed to determine the true value of metabolic or bariatric surgery such as gastric bypass, compared with medical treatment for type 2 diabetes. Studies of bariatric surgery in the nondiabetic population found it was most cost-effective in the following scenarios: in women; in the morbidly obese vs. the moderately obese; in patients with obesity-related comorbidities including diabetes; when the procedures were performed laparoscopically; and when the studies themselves received industry support.

In people with diabetes, the results were similar. “Diabetes metabolic surgery is more cost-effective early in the course of type 2 diabetes compared to later in the course, when performed laparoscopically, and again when the study received support from industry,” reported Dr. William H. Herman, professor of epidemiology and internal medicine at the University of Michigan School of Public Health in Ann Arbor and director of the Michigan Center for Diabetes Translational Research.

He reviewed 11 economic analyses of bariatric surgery and concluded that all exceeded the benchmark for cost-effectiveness based on the cost per quality-adjusted life-year (QALY) gained. Six studies evaluated the general population of obese people and found that the cost-effectiveness ratios ranged from $1,600 to $44,000 per QALY gained. The remaining five studies involved obese patients with type 2 diabetes, two of which reported cost-effectiveness ratios of $2,000 to $23,000 per QALY gained; and the remaining three studies actually reporting a cost-savings. “In other words, the money spent on these interventions was more than recouped in the savings resulting from reduced downstream medical costs,” Dr. Herman reported at the American Diabetes Association scientific sessions.

The studies that found gastric bypass cost-saving in diabetes are noteworthy, Dr. Herman said. “If an intervention is more effective and less costly than a comparator intervention, then it is cost-saving, and that really is an unusual finding in health or medicine; perhaps 10% or 15% of interventions turn out to be cost-saving,” he said. “These are interventions that we want to adopt and put into practice pretty much without question.”

By the same measure, if an intervention is more costly and less effective, it’s easy to dismiss “out of hand,” Dr. Herman said. However, interpreting some of the studies he evaluated was more nuanced. “The problem occurs when a new treatment is both more effective but more costly, which was the case with two of the five analyses of metabolic surgery, and all of the analysis of bariatric surgery in the nondiabetic population,” he said

While gastric bypass surgery for type 2 diabetes is a good value, Dr. Herman added a few caveats. “When one looks at other interventions in similar categories, metformin for diabetes prevention has recently been shown to be cost-saving,” he said. He also said surgery is more cost-effective than marginally cost-effective interventions like intensive glycemic management for people with newly diagnosed type 2 diabetes or retinal screening every year vs. every 2 years.

One key issue with the existing evidence on cost-effectiveness of metabolic surgery for type 2 diabetes that Dr. Herman elucidated is how the studies accounted for participants lost to follow-up. “We know that a patient lost to follow-up may have a less favorable outcome than one who returns for follow-up,” he said. There are two ways studies can account for lost patients: the available-case analysis, which assumes that the patients lost to follow-up have the same rates of remission; and the attrition-adjusted available case follow-up, which uses a worst-case imputation. “I would argue that to account for attrition bias, remission rates calculated using the cases available for follow-up should be adjusted using worst-case imputation,” Dr. Herman said.

He pointed out another limitation when calculating the value of gastric bypass surgery for type 2 diabetes: “There are no randomized clinical trials of metabolic surgery that describe its long-term impact on diabetes treatments, complications, comorbidities, and survival. And it really is going be very important to get these data to confirm the cost-effectiveness of metabolic surgery.”

Among the shortcomings of the existing literature he noted are the assumptions that treatment-related adverse events are self-limited, that body mass index (BMI) achieved up to 5 years after surgery will remain stable, and that diabetes will not relapse. “The data are pretty good now on reversal, remission, hernia repair, and those sorts of things, but we need to look at longer downstream costs associated with surgery, including the need for cholecystectomy, joint replacements, and nutritional deficiencies that may occur and do clearly have financial implications,” he said.

At the same time, the analyses on gastric bypass surgery for type 2 diabetes could be more favorable if they account for improvements in health-related quality-of-life and rely less on cross-sectional data. Dr. Herman said, “I would argue that using cross-sectional data to estimate changes in health-related quality of life as a function of BMI underestimates the improvements on health-related quality-of-life associated with weight loss and will in fact underestimate the cost utility of interventions for obesity treatment,” he said.

Dr. Herman added, “Clearly the evidence to date suggests that metabolic surgery is cost-effective, but I’ll be more assured when I see longer-term follow-up.”

Dr. Herman has no financial relationships to disclose.

NEW ORLEANS – If the yardstick for measuring the cost-effectiveness of an operation or a medical treatment is that it costs less than $50,000 for each quality-adjusted life-year gained, then weight-loss surgery as a treatment for type 2 diabetes is cost-effective.

However, more long-term follow-up is needed to determine the true value of metabolic or bariatric surgery such as gastric bypass, compared with medical treatment for type 2 diabetes. Studies of bariatric surgery in the nondiabetic population found it was most cost-effective in the following scenarios: in women; in the morbidly obese vs. the moderately obese; in patients with obesity-related comorbidities including diabetes; when the procedures were performed laparoscopically; and when the studies themselves received industry support.

In people with diabetes, the results were similar. “Diabetes metabolic surgery is more cost-effective early in the course of type 2 diabetes compared to later in the course, when performed laparoscopically, and again when the study received support from industry,” reported Dr. William H. Herman, professor of epidemiology and internal medicine at the University of Michigan School of Public Health in Ann Arbor and director of the Michigan Center for Diabetes Translational Research.

He reviewed 11 economic analyses of bariatric surgery and concluded that all exceeded the benchmark for cost-effectiveness based on the cost per quality-adjusted life-year (QALY) gained. Six studies evaluated the general population of obese people and found that the cost-effectiveness ratios ranged from $1,600 to $44,000 per QALY gained. The remaining five studies involved obese patients with type 2 diabetes, two of which reported cost-effectiveness ratios of $2,000 to $23,000 per QALY gained; and the remaining three studies actually reporting a cost-savings. “In other words, the money spent on these interventions was more than recouped in the savings resulting from reduced downstream medical costs,” Dr. Herman reported at the American Diabetes Association scientific sessions.

The studies that found gastric bypass cost-saving in diabetes are noteworthy, Dr. Herman said. “If an intervention is more effective and less costly than a comparator intervention, then it is cost-saving, and that really is an unusual finding in health or medicine; perhaps 10% or 15% of interventions turn out to be cost-saving,” he said. “These are interventions that we want to adopt and put into practice pretty much without question.”

By the same measure, if an intervention is more costly and less effective, it’s easy to dismiss “out of hand,” Dr. Herman said. However, interpreting some of the studies he evaluated was more nuanced. “The problem occurs when a new treatment is both more effective but more costly, which was the case with two of the five analyses of metabolic surgery, and all of the analysis of bariatric surgery in the nondiabetic population,” he said

While gastric bypass surgery for type 2 diabetes is a good value, Dr. Herman added a few caveats. “When one looks at other interventions in similar categories, metformin for diabetes prevention has recently been shown to be cost-saving,” he said. He also said surgery is more cost-effective than marginally cost-effective interventions like intensive glycemic management for people with newly diagnosed type 2 diabetes or retinal screening every year vs. every 2 years.

One key issue with the existing evidence on cost-effectiveness of metabolic surgery for type 2 diabetes that Dr. Herman elucidated is how the studies accounted for participants lost to follow-up. “We know that a patient lost to follow-up may have a less favorable outcome than one who returns for follow-up,” he said. There are two ways studies can account for lost patients: the available-case analysis, which assumes that the patients lost to follow-up have the same rates of remission; and the attrition-adjusted available case follow-up, which uses a worst-case imputation. “I would argue that to account for attrition bias, remission rates calculated using the cases available for follow-up should be adjusted using worst-case imputation,” Dr. Herman said.

He pointed out another limitation when calculating the value of gastric bypass surgery for type 2 diabetes: “There are no randomized clinical trials of metabolic surgery that describe its long-term impact on diabetes treatments, complications, comorbidities, and survival. And it really is going be very important to get these data to confirm the cost-effectiveness of metabolic surgery.”

Among the shortcomings of the existing literature he noted are the assumptions that treatment-related adverse events are self-limited, that body mass index (BMI) achieved up to 5 years after surgery will remain stable, and that diabetes will not relapse. “The data are pretty good now on reversal, remission, hernia repair, and those sorts of things, but we need to look at longer downstream costs associated with surgery, including the need for cholecystectomy, joint replacements, and nutritional deficiencies that may occur and do clearly have financial implications,” he said.

At the same time, the analyses on gastric bypass surgery for type 2 diabetes could be more favorable if they account for improvements in health-related quality-of-life and rely less on cross-sectional data. Dr. Herman said, “I would argue that using cross-sectional data to estimate changes in health-related quality of life as a function of BMI underestimates the improvements on health-related quality-of-life associated with weight loss and will in fact underestimate the cost utility of interventions for obesity treatment,” he said.

Dr. Herman added, “Clearly the evidence to date suggests that metabolic surgery is cost-effective, but I’ll be more assured when I see longer-term follow-up.”

Dr. Herman has no financial relationships to disclose.

NEW ORLEANS – If the yardstick for measuring the cost-effectiveness of an operation or a medical treatment is that it costs less than $50,000 for each quality-adjusted life-year gained, then weight-loss surgery as a treatment for type 2 diabetes is cost-effective.

However, more long-term follow-up is needed to determine the true value of metabolic or bariatric surgery such as gastric bypass, compared with medical treatment for type 2 diabetes. Studies of bariatric surgery in the nondiabetic population found it was most cost-effective in the following scenarios: in women; in the morbidly obese vs. the moderately obese; in patients with obesity-related comorbidities including diabetes; when the procedures were performed laparoscopically; and when the studies themselves received industry support.

In people with diabetes, the results were similar. “Diabetes metabolic surgery is more cost-effective early in the course of type 2 diabetes compared to later in the course, when performed laparoscopically, and again when the study received support from industry,” reported Dr. William H. Herman, professor of epidemiology and internal medicine at the University of Michigan School of Public Health in Ann Arbor and director of the Michigan Center for Diabetes Translational Research.

He reviewed 11 economic analyses of bariatric surgery and concluded that all exceeded the benchmark for cost-effectiveness based on the cost per quality-adjusted life-year (QALY) gained. Six studies evaluated the general population of obese people and found that the cost-effectiveness ratios ranged from $1,600 to $44,000 per QALY gained. The remaining five studies involved obese patients with type 2 diabetes, two of which reported cost-effectiveness ratios of $2,000 to $23,000 per QALY gained; and the remaining three studies actually reporting a cost-savings. “In other words, the money spent on these interventions was more than recouped in the savings resulting from reduced downstream medical costs,” Dr. Herman reported at the American Diabetes Association scientific sessions.

The studies that found gastric bypass cost-saving in diabetes are noteworthy, Dr. Herman said. “If an intervention is more effective and less costly than a comparator intervention, then it is cost-saving, and that really is an unusual finding in health or medicine; perhaps 10% or 15% of interventions turn out to be cost-saving,” he said. “These are interventions that we want to adopt and put into practice pretty much without question.”

By the same measure, if an intervention is more costly and less effective, it’s easy to dismiss “out of hand,” Dr. Herman said. However, interpreting some of the studies he evaluated was more nuanced. “The problem occurs when a new treatment is both more effective but more costly, which was the case with two of the five analyses of metabolic surgery, and all of the analysis of bariatric surgery in the nondiabetic population,” he said

While gastric bypass surgery for type 2 diabetes is a good value, Dr. Herman added a few caveats. “When one looks at other interventions in similar categories, metformin for diabetes prevention has recently been shown to be cost-saving,” he said. He also said surgery is more cost-effective than marginally cost-effective interventions like intensive glycemic management for people with newly diagnosed type 2 diabetes or retinal screening every year vs. every 2 years.

One key issue with the existing evidence on cost-effectiveness of metabolic surgery for type 2 diabetes that Dr. Herman elucidated is how the studies accounted for participants lost to follow-up. “We know that a patient lost to follow-up may have a less favorable outcome than one who returns for follow-up,” he said. There are two ways studies can account for lost patients: the available-case analysis, which assumes that the patients lost to follow-up have the same rates of remission; and the attrition-adjusted available case follow-up, which uses a worst-case imputation. “I would argue that to account for attrition bias, remission rates calculated using the cases available for follow-up should be adjusted using worst-case imputation,” Dr. Herman said.

He pointed out another limitation when calculating the value of gastric bypass surgery for type 2 diabetes: “There are no randomized clinical trials of metabolic surgery that describe its long-term impact on diabetes treatments, complications, comorbidities, and survival. And it really is going be very important to get these data to confirm the cost-effectiveness of metabolic surgery.”

Among the shortcomings of the existing literature he noted are the assumptions that treatment-related adverse events are self-limited, that body mass index (BMI) achieved up to 5 years after surgery will remain stable, and that diabetes will not relapse. “The data are pretty good now on reversal, remission, hernia repair, and those sorts of things, but we need to look at longer downstream costs associated with surgery, including the need for cholecystectomy, joint replacements, and nutritional deficiencies that may occur and do clearly have financial implications,” he said.

At the same time, the analyses on gastric bypass surgery for type 2 diabetes could be more favorable if they account for improvements in health-related quality-of-life and rely less on cross-sectional data. Dr. Herman said, “I would argue that using cross-sectional data to estimate changes in health-related quality of life as a function of BMI underestimates the improvements on health-related quality-of-life associated with weight loss and will in fact underestimate the cost utility of interventions for obesity treatment,” he said.

Dr. Herman added, “Clearly the evidence to date suggests that metabolic surgery is cost-effective, but I’ll be more assured when I see longer-term follow-up.”

Dr. Herman has no financial relationships to disclose.

NEW ORLEANS – Having people with type 2 diabetes mellitus use an artificial pancreas during hospitalization has the potential to improve control of their glycemia when compared with conventional insulin therapy, based on the results of a small study of inpatients in the United Kingdom.

“This is the first study to show that automated subcutaneous closed-loop insulin delivery without meal-time insulin is feasible and safe in patients with insulin-treated type 2 diabetes in the general wards,” Dr. Hood Thabit of the University of Cambridge (England) reported at the ADA annual scientific sessions. “Closed-loop [delivery] increased time in target, with reduced glucose variability and reduced time spent hyperglycemic without actually increasing time spent hypoglycemic,” he said.

The study involved 40 general ward inpatients evenly assigned to the closed-loop system and conventional insulin therapy for 72 hours.

Dr. Thabit said hyperglycemia in hospital patients is a common problem that’s poorly managed. “There’s an unmet need for an effective and safe glucose control, specifically in the underserved and understudied population of type 2 diabetes in the general wards,” he said. The use of the closed-loop system in inpatients with type 2 diabetes “remains untested until now,” Dr. Thabit added.

The 20 patients randomized to the closed-loop system spent an average of 61% of the whole study period within the sensor glucose target vs. 38% of those on conventional insulin therapy. The closed-loop patients also used comparable insulin daily on average: 62.6 U (±36.3 U) vs. 66.0 U (±39.6 U), Dr. Thabit said.

He noted that those on the closed-loop system did not have to announce meals to the control algorithm, or give any meal-time insulin – “we didn’t want to trouble our nurses with this, due to the increasing workload that health care professionals in the hospital currently face,” he said – and showed “significantly improved” nighttime control of glucose while “simultaneously reducing the risk of nocturnal hypoglycemia”. “The closed loop may potentially be an effective and safe tool to manage hospital inpatient hyperglycemia in this particularly underserved population of patients whilst easing the burden of health care professionals in hospital,” he said.

The cost is not insignificant. The pump and sensor devices together with related consumables can cost up to £6,000 (about $8,600), but he did note the artificial pancreas device itself is reusable. The cost of the automated closed-loop glucose control system can also potentially be offset by the reduced time of health care professionals spent managing inpatient hyperglycemia safely. The study investigators are in the process of planning a larger trial, Dr. Thabit said.

Dr. Thabit had no financial disclosures. Some coauthors disclosed relationships with Novo Nordisk; Medtronic MiniMed; Becton, Dickinson and Co.; Abbott Diabetes Care; Roche Pharmaceuticals; Cell Novo; Animas; Eli Lilly; B. Braun Melsungen; Sanofi-Aventis Deutschland; and Profil Institute for Clinical Research.

NEW ORLEANS – Having people with type 2 diabetes mellitus use an artificial pancreas during hospitalization has the potential to improve control of their glycemia when compared with conventional insulin therapy, based on the results of a small study of inpatients in the United Kingdom.

“This is the first study to show that automated subcutaneous closed-loop insulin delivery without meal-time insulin is feasible and safe in patients with insulin-treated type 2 diabetes in the general wards,” Dr. Hood Thabit of the University of Cambridge (England) reported at the ADA annual scientific sessions. “Closed-loop [delivery] increased time in target, with reduced glucose variability and reduced time spent hyperglycemic without actually increasing time spent hypoglycemic,” he said.

The study involved 40 general ward inpatients evenly assigned to the closed-loop system and conventional insulin therapy for 72 hours.

Dr. Thabit said hyperglycemia in hospital patients is a common problem that’s poorly managed. “There’s an unmet need for an effective and safe glucose control, specifically in the underserved and understudied population of type 2 diabetes in the general wards,” he said. The use of the closed-loop system in inpatients with type 2 diabetes “remains untested until now,” Dr. Thabit added.

The 20 patients randomized to the closed-loop system spent an average of 61% of the whole study period within the sensor glucose target vs. 38% of those on conventional insulin therapy. The closed-loop patients also used comparable insulin daily on average: 62.6 U (±36.3 U) vs. 66.0 U (±39.6 U), Dr. Thabit said.

He noted that those on the closed-loop system did not have to announce meals to the control algorithm, or give any meal-time insulin – “we didn’t want to trouble our nurses with this, due to the increasing workload that health care professionals in the hospital currently face,” he said – and showed “significantly improved” nighttime control of glucose while “simultaneously reducing the risk of nocturnal hypoglycemia”. “The closed loop may potentially be an effective and safe tool to manage hospital inpatient hyperglycemia in this particularly underserved population of patients whilst easing the burden of health care professionals in hospital,” he said.

The cost is not insignificant. The pump and sensor devices together with related consumables can cost up to £6,000 (about $8,600), but he did note the artificial pancreas device itself is reusable. The cost of the automated closed-loop glucose control system can also potentially be offset by the reduced time of health care professionals spent managing inpatient hyperglycemia safely. The study investigators are in the process of planning a larger trial, Dr. Thabit said.

Dr. Thabit had no financial disclosures. Some coauthors disclosed relationships with Novo Nordisk; Medtronic MiniMed; Becton, Dickinson and Co.; Abbott Diabetes Care; Roche Pharmaceuticals; Cell Novo; Animas; Eli Lilly; B. Braun Melsungen; Sanofi-Aventis Deutschland; and Profil Institute for Clinical Research.

NEW ORLEANS – Having people with type 2 diabetes mellitus use an artificial pancreas during hospitalization has the potential to improve control of their glycemia when compared with conventional insulin therapy, based on the results of a small study of inpatients in the United Kingdom.

“This is the first study to show that automated subcutaneous closed-loop insulin delivery without meal-time insulin is feasible and safe in patients with insulin-treated type 2 diabetes in the general wards,” Dr. Hood Thabit of the University of Cambridge (England) reported at the ADA annual scientific sessions. “Closed-loop [delivery] increased time in target, with reduced glucose variability and reduced time spent hyperglycemic without actually increasing time spent hypoglycemic,” he said.

The study involved 40 general ward inpatients evenly assigned to the closed-loop system and conventional insulin therapy for 72 hours.

Dr. Thabit said hyperglycemia in hospital patients is a common problem that’s poorly managed. “There’s an unmet need for an effective and safe glucose control, specifically in the underserved and understudied population of type 2 diabetes in the general wards,” he said. The use of the closed-loop system in inpatients with type 2 diabetes “remains untested until now,” Dr. Thabit added.

The 20 patients randomized to the closed-loop system spent an average of 61% of the whole study period within the sensor glucose target vs. 38% of those on conventional insulin therapy. The closed-loop patients also used comparable insulin daily on average: 62.6 U (±36.3 U) vs. 66.0 U (±39.6 U), Dr. Thabit said.

He noted that those on the closed-loop system did not have to announce meals to the control algorithm, or give any meal-time insulin – “we didn’t want to trouble our nurses with this, due to the increasing workload that health care professionals in the hospital currently face,” he said – and showed “significantly improved” nighttime control of glucose while “simultaneously reducing the risk of nocturnal hypoglycemia”. “The closed loop may potentially be an effective and safe tool to manage hospital inpatient hyperglycemia in this particularly underserved population of patients whilst easing the burden of health care professionals in hospital,” he said.

The cost is not insignificant. The pump and sensor devices together with related consumables can cost up to £6,000 (about $8,600), but he did note the artificial pancreas device itself is reusable. The cost of the automated closed-loop glucose control system can also potentially be offset by the reduced time of health care professionals spent managing inpatient hyperglycemia safely. The study investigators are in the process of planning a larger trial, Dr. Thabit said.

Dr. Thabit had no financial disclosures. Some coauthors disclosed relationships with Novo Nordisk; Medtronic MiniMed; Becton, Dickinson and Co.; Abbott Diabetes Care; Roche Pharmaceuticals; Cell Novo; Animas; Eli Lilly; B. Braun Melsungen; Sanofi-Aventis Deutschland; and Profil Institute for Clinical Research.

When a patient undergoes aortic valve replacement for infective endocarditis, conventional thinking holds that cardiac surgeons should use homografts because they have greater resistance to infection, but a recent study of more than 300 cases at two academic medical centers concluded that homografts may not necessarily offer such a benefit.

The study, published in the June issue of the Journal of Thoracic and Cardiovascular Surgery (2016;151:1239-48), involved 304 consecutive adult patients on whom 30-40 different surgeons performed operations for active infective endocarditis (IE) in the aortic valve from 2002 to 2014.

©CDC/Janice Haney Carr

“Our findings suggest that patient-specific factors, such as age and implant preference, as well as technical reconstructive considerations, should drive prosthetic choice, rather than surgical dogma,” said Joon Bum Kim, Ph.D., of Massachusetts General Hospital, Harvard Medical School, both in Boston, and Asan Medical Center in Seoul, Korea, and his colleagues.

The study found that cardiac surgeons favored homografts over conventional prostheses when the patient had prosthetic valve endocarditis (58.1% vs. 28.8%) and methicillin-resistant Staphylococcus aureus (25.6% vs. 12.1%), both significant differences.

“No significant benefit to the use of homografts was demonstrable with regard to resistance to reinfection in the setting of IE,” Dr. Kim and his colleagues said.

Because reinfection after valve replacement for IE is such a strong concern, the debate over which prosthesis is best has ensued for decades. The researchers pointed out that the evidence favoring autologous or allogeneic tissue over synthetic material in the infective field is weak, mostly built on single-armed observational studies without comparison to conventional prosthesis.

With that in mind, the researchers pooled data from two institutions to compare short- and long-term results for homograft vs. conventional prosthetic valves in patients with IE. In this study group, 86 (28.3%) had homografts, 139 (45.7%) had xenograft prostheses, and 79 (26%) mechanical prostheses. The homograft group had more than twice the rate of early death than did the conventional group – 19.8% vs. 9.2%, a significant difference (P = .019).

During follow-up, which ranged from 4.7 to 72.6 months, 60 patients (19.7%) of the total group died and 23 (7.7%) experienced reinfection, but rates did not vary between the homograft and conventional prosthesis groups, Dr. Kim and his colleagues reported.

Demographics were similar between the three groups with a few exceptions Those who received the mechanical prostheses were younger (mean age, 47.2 years vs. 55.6 and 59.8 for the homograft and xenograft groups, respectively), had lower rates of diabetes (5.1% vs. 10.5% and 12.2%) and had less-severe disease based on New York Heart Association functional class III or IV scores (34.2% vs. 54.7% and 53.2%). The types of IE pathogens also differed among the three groups; methicillin-resistant staphylococci was most common in the homograft group (25.6%), whereas the viridans group streptococci was the leading cause of IE in the mechanical (38% ) and xenograft groups (25.2% ).

The use of homografts involves a highly complex operation, typically requiring a complete aortic root replacement, which “may be the major drawback in recommending it to patients already at high risk of operative mortality,” the investigators wrote. The durability of homografts makes their use limited for younger patients, and such grafts are somewhat scarce and require cryopreservation. “Therefore, the notion that homografts are required may in practice present an obstacle to appropriate surgical management of patients who have IE,” Dr. Kim and his coauthors wrote. All patients but one in the homograft group received aortic arch replacement (98.8%) whereas 30 of the patients in the conventional group did so (13.8%).

The study findings are consistent with an earlier comparative study (Ann. Thorac. Surg. 2012;93:480-07), according to Dr. Kim and his colleagues. “These findings suggest that patient-specific factors, such as patient preferences and technical considerations, should be the principal drivers of choices of valve prostheses,” they said. “Furthermore, lack of access to homografts should not be considered an obstacle to surgical therapy for this serious condition.”

Coauthor Dr. Sundt disclosed that he is a consultant for Thrasos Therapeutics. Dr. Kim and the other coauthors had no financial disclosures. 

When a patient undergoes aortic valve replacement for infective endocarditis, conventional thinking holds that cardiac surgeons should use homografts because they have greater resistance to infection, but a recent study of more than 300 cases at two academic medical centers concluded that homografts may not necessarily offer such a benefit.

The study, published in the June issue of the Journal of Thoracic and Cardiovascular Surgery (2016;151:1239-48), involved 304 consecutive adult patients on whom 30-40 different surgeons performed operations for active infective endocarditis (IE) in the aortic valve from 2002 to 2014.

©CDC/Janice Haney Carr

“Our findings suggest that patient-specific factors, such as age and implant preference, as well as technical reconstructive considerations, should drive prosthetic choice, rather than surgical dogma,” said Joon Bum Kim, Ph.D., of Massachusetts General Hospital, Harvard Medical School, both in Boston, and Asan Medical Center in Seoul, Korea, and his colleagues.

The study found that cardiac surgeons favored homografts over conventional prostheses when the patient had prosthetic valve endocarditis (58.1% vs. 28.8%) and methicillin-resistant Staphylococcus aureus (25.6% vs. 12.1%), both significant differences.

“No significant benefit to the use of homografts was demonstrable with regard to resistance to reinfection in the setting of IE,” Dr. Kim and his colleagues said.

Because reinfection after valve replacement for IE is such a strong concern, the debate over which prosthesis is best has ensued for decades. The researchers pointed out that the evidence favoring autologous or allogeneic tissue over synthetic material in the infective field is weak, mostly built on single-armed observational studies without comparison to conventional prosthesis.

With that in mind, the researchers pooled data from two institutions to compare short- and long-term results for homograft vs. conventional prosthetic valves in patients with IE. In this study group, 86 (28.3%) had homografts, 139 (45.7%) had xenograft prostheses, and 79 (26%) mechanical prostheses. The homograft group had more than twice the rate of early death than did the conventional group – 19.8% vs. 9.2%, a significant difference (P = .019).

During follow-up, which ranged from 4.7 to 72.6 months, 60 patients (19.7%) of the total group died and 23 (7.7%) experienced reinfection, but rates did not vary between the homograft and conventional prosthesis groups, Dr. Kim and his colleagues reported.

Demographics were similar between the three groups with a few exceptions Those who received the mechanical prostheses were younger (mean age, 47.2 years vs. 55.6 and 59.8 for the homograft and xenograft groups, respectively), had lower rates of diabetes (5.1% vs. 10.5% and 12.2%) and had less-severe disease based on New York Heart Association functional class III or IV scores (34.2% vs. 54.7% and 53.2%). The types of IE pathogens also differed among the three groups; methicillin-resistant staphylococci was most common in the homograft group (25.6%), whereas the viridans group streptococci was the leading cause of IE in the mechanical (38% ) and xenograft groups (25.2% ).

The use of homografts involves a highly complex operation, typically requiring a complete aortic root replacement, which “may be the major drawback in recommending it to patients already at high risk of operative mortality,” the investigators wrote. The durability of homografts makes their use limited for younger patients, and such grafts are somewhat scarce and require cryopreservation. “Therefore, the notion that homografts are required may in practice present an obstacle to appropriate surgical management of patients who have IE,” Dr. Kim and his coauthors wrote. All patients but one in the homograft group received aortic arch replacement (98.8%) whereas 30 of the patients in the conventional group did so (13.8%).

The study findings are consistent with an earlier comparative study (Ann. Thorac. Surg. 2012;93:480-07), according to Dr. Kim and his colleagues. “These findings suggest that patient-specific factors, such as patient preferences and technical considerations, should be the principal drivers of choices of valve prostheses,” they said. “Furthermore, lack of access to homografts should not be considered an obstacle to surgical therapy for this serious condition.”

Coauthor Dr. Sundt disclosed that he is a consultant for Thrasos Therapeutics. Dr. Kim and the other coauthors had no financial disclosures. 

When a patient undergoes aortic valve replacement for infective endocarditis, conventional thinking holds that cardiac surgeons should use homografts because they have greater resistance to infection, but a recent study of more than 300 cases at two academic medical centers concluded that homografts may not necessarily offer such a benefit.

The study, published in the June issue of the Journal of Thoracic and Cardiovascular Surgery (2016;151:1239-48), involved 304 consecutive adult patients on whom 30-40 different surgeons performed operations for active infective endocarditis (IE) in the aortic valve from 2002 to 2014.

©CDC/Janice Haney Carr

“Our findings suggest that patient-specific factors, such as age and implant preference, as well as technical reconstructive considerations, should drive prosthetic choice, rather than surgical dogma,” said Joon Bum Kim, Ph.D., of Massachusetts General Hospital, Harvard Medical School, both in Boston, and Asan Medical Center in Seoul, Korea, and his colleagues.

The study found that cardiac surgeons favored homografts over conventional prostheses when the patient had prosthetic valve endocarditis (58.1% vs. 28.8%) and methicillin-resistant Staphylococcus aureus (25.6% vs. 12.1%), both significant differences.

“No significant benefit to the use of homografts was demonstrable with regard to resistance to reinfection in the setting of IE,” Dr. Kim and his colleagues said.

Because reinfection after valve replacement for IE is such a strong concern, the debate over which prosthesis is best has ensued for decades. The researchers pointed out that the evidence favoring autologous or allogeneic tissue over synthetic material in the infective field is weak, mostly built on single-armed observational studies without comparison to conventional prosthesis.

With that in mind, the researchers pooled data from two institutions to compare short- and long-term results for homograft vs. conventional prosthetic valves in patients with IE. In this study group, 86 (28.3%) had homografts, 139 (45.7%) had xenograft prostheses, and 79 (26%) mechanical prostheses. The homograft group had more than twice the rate of early death than did the conventional group – 19.8% vs. 9.2%, a significant difference (P = .019).

During follow-up, which ranged from 4.7 to 72.6 months, 60 patients (19.7%) of the total group died and 23 (7.7%) experienced reinfection, but rates did not vary between the homograft and conventional prosthesis groups, Dr. Kim and his colleagues reported.

Demographics were similar between the three groups with a few exceptions Those who received the mechanical prostheses were younger (mean age, 47.2 years vs. 55.6 and 59.8 for the homograft and xenograft groups, respectively), had lower rates of diabetes (5.1% vs. 10.5% and 12.2%) and had less-severe disease based on New York Heart Association functional class III or IV scores (34.2% vs. 54.7% and 53.2%). The types of IE pathogens also differed among the three groups; methicillin-resistant staphylococci was most common in the homograft group (25.6%), whereas the viridans group streptococci was the leading cause of IE in the mechanical (38% ) and xenograft groups (25.2% ).

The use of homografts involves a highly complex operation, typically requiring a complete aortic root replacement, which “may be the major drawback in recommending it to patients already at high risk of operative mortality,” the investigators wrote. The durability of homografts makes their use limited for younger patients, and such grafts are somewhat scarce and require cryopreservation. “Therefore, the notion that homografts are required may in practice present an obstacle to appropriate surgical management of patients who have IE,” Dr. Kim and his coauthors wrote. All patients but one in the homograft group received aortic arch replacement (98.8%) whereas 30 of the patients in the conventional group did so (13.8%).

The study findings are consistent with an earlier comparative study (Ann. Thorac. Surg. 2012;93:480-07), according to Dr. Kim and his colleagues. “These findings suggest that patient-specific factors, such as patient preferences and technical considerations, should be the principal drivers of choices of valve prostheses,” they said. “Furthermore, lack of access to homografts should not be considered an obstacle to surgical therapy for this serious condition.”

Coauthor Dr. Sundt disclosed that he is a consultant for Thrasos Therapeutics. Dr. Kim and the other coauthors had no financial disclosures. 

Infections of aortic prosthetic grafts can be a devastating complication, and while cryopreserved human allografts (CHA) can continue to possess antibacterial activity even after 5 years or more in storage, cardiac surgeons may want to apply additional antibiotic agents during implantation to boost bacterial resistance, investigators from Germany reported in the May issue of the Journal of Thoracic and Cardiovascular Surgery (2016;151:1251-9).

The researchers compared three different antibiotic regimens used in processing CHA aortic tissue and valves to determine the impact each can have on long-term bacterial resistance.

©CDC/Janice Haney Carr

“Antibiotic combinations applied during CHA processing have a significant influence on their infection resistance,” said Dr. Viola Steffen of Hannover (Germany) Medical School and her colleagues. The average storage time of CHAs was 8.5 years, with the longest having been stored for 10 years.

The study involved microbiologic tests in vitro of three different antibiotic regimens used in processing CHA: gentamicin-piperacillin-vancomycin-metronidazole-amphotericin B (group A); gentamicin-piperacillin-flucloxacillin-metronidazole-amphotericin B (group B); and meropenem-vancomycin-tobramycin-colistin-amphotericin B (group C). The combinations are used to counteract Staphylococcus epidermidis and Staphylococcus aureus.

The study exposed pieces of 10 CHAs to different microbes and determined that regimen groups B and C were more effective than group A in eradicating gram-positive organisms. Specifically, group C was most resistant to Escherichia coli, whereas group B was most effective against Pseudomonas aeruginosa. Aortic tissue showed significantly less contamination with staphylococcal bacteria than valve grafts, the study reported.

Dr. Steffen and her colleagues said that tissue banks use antibiotic protocols during CHA processing, but they differ substantially. “Our results support the hypothesis that infection resistance of CHAs depends on the antibiotic pretreatment during processing and their residual activity,” they said.

The study had four key findings:

• The infection resistance of aortic wall and valve tissue differed significantly.

• In aortic wall specimens, group A specimens exhibited increased adherence of S. epidermidis, with vancomycin in group A and flucloxacillin in group B being the only differentiating agents between the two.

• Cryopreserved aortic vessels had a propensity toward reduced infection resistance against P. aeruginosa.

• Morphologic changes occurred in the microorganisms, especially rod-shaped E. coli, indicating that regional antibiotic release alters bacterial growth without eliminating all adherent bacteria.

Dr. Steffen and her colleagues noted that while previous studies determined that residual concentrations of antibiotics used in processing CHA heart valves and blood vessels are still present after they are prepared for implantation, they neither measured the antibacterial affect, clarified the period of cryopreservation nor differentiated between valve and vessel tissue (PLoS One. 2014;9:e112679; Transfus Med Hemother. 2011;38:379-86).

The Hannover researchers found that only a few gram-positive microorganisms adhered to aortic wall specimens, although they found “extensive adherence” of S. epidermidis in group A specimens. Valves, however, “were completely colonized” with both strains of staphylococcal bacteria, although the severity of contamination varied depending on the regimen used.

The findings raise some questions about the antibiotic properties of CHAs. “Because their infection resistance depends on the antibiotic combination selected during processing, further investigations concerning this treatment are necessary to improve the antimicrobial activity against frequent and highly virulent infection-causing bacteria,” Dr. Steffen and her colleagues said.

Dr. Steffen and her coauthors had no financial relationships to disclose.

Infections of aortic prosthetic grafts can be a devastating complication, and while cryopreserved human allografts (CHA) can continue to possess antibacterial activity even after 5 years or more in storage, cardiac surgeons may want to apply additional antibiotic agents during implantation to boost bacterial resistance, investigators from Germany reported in the May issue of the Journal of Thoracic and Cardiovascular Surgery (2016;151:1251-9).

The researchers compared three different antibiotic regimens used in processing CHA aortic tissue and valves to determine the impact each can have on long-term bacterial resistance.

©CDC/Janice Haney Carr

“Antibiotic combinations applied during CHA processing have a significant influence on their infection resistance,” said Dr. Viola Steffen of Hannover (Germany) Medical School and her colleagues. The average storage time of CHAs was 8.5 years, with the longest having been stored for 10 years.

The study involved microbiologic tests in vitro of three different antibiotic regimens used in processing CHA: gentamicin-piperacillin-vancomycin-metronidazole-amphotericin B (group A); gentamicin-piperacillin-flucloxacillin-metronidazole-amphotericin B (group B); and meropenem-vancomycin-tobramycin-colistin-amphotericin B (group C). The combinations are used to counteract Staphylococcus epidermidis and Staphylococcus aureus.

The study exposed pieces of 10 CHAs to different microbes and determined that regimen groups B and C were more effective than group A in eradicating gram-positive organisms. Specifically, group C was most resistant to Escherichia coli, whereas group B was most effective against Pseudomonas aeruginosa. Aortic tissue showed significantly less contamination with staphylococcal bacteria than valve grafts, the study reported.

Dr. Steffen and her colleagues said that tissue banks use antibiotic protocols during CHA processing, but they differ substantially. “Our results support the hypothesis that infection resistance of CHAs depends on the antibiotic pretreatment during processing and their residual activity,” they said.

The study had four key findings:

• The infection resistance of aortic wall and valve tissue differed significantly.

• In aortic wall specimens, group A specimens exhibited increased adherence of S. epidermidis, with vancomycin in group A and flucloxacillin in group B being the only differentiating agents between the two.

• Cryopreserved aortic vessels had a propensity toward reduced infection resistance against P. aeruginosa.

• Morphologic changes occurred in the microorganisms, especially rod-shaped E. coli, indicating that regional antibiotic release alters bacterial growth without eliminating all adherent bacteria.

Dr. Steffen and her colleagues noted that while previous studies determined that residual concentrations of antibiotics used in processing CHA heart valves and blood vessels are still present after they are prepared for implantation, they neither measured the antibacterial affect, clarified the period of cryopreservation nor differentiated between valve and vessel tissue (PLoS One. 2014;9:e112679; Transfus Med Hemother. 2011;38:379-86).

The Hannover researchers found that only a few gram-positive microorganisms adhered to aortic wall specimens, although they found “extensive adherence” of S. epidermidis in group A specimens. Valves, however, “were completely colonized” with both strains of staphylococcal bacteria, although the severity of contamination varied depending on the regimen used.

The findings raise some questions about the antibiotic properties of CHAs. “Because their infection resistance depends on the antibiotic combination selected during processing, further investigations concerning this treatment are necessary to improve the antimicrobial activity against frequent and highly virulent infection-causing bacteria,” Dr. Steffen and her colleagues said.

Dr. Steffen and her coauthors had no financial relationships to disclose.

Infections of aortic prosthetic grafts can be a devastating complication, and while cryopreserved human allografts (CHA) can continue to possess antibacterial activity even after 5 years or more in storage, cardiac surgeons may want to apply additional antibiotic agents during implantation to boost bacterial resistance, investigators from Germany reported in the May issue of the Journal of Thoracic and Cardiovascular Surgery (2016;151:1251-9).

The researchers compared three different antibiotic regimens used in processing CHA aortic tissue and valves to determine the impact each can have on long-term bacterial resistance.

©CDC/Janice Haney Carr

“Antibiotic combinations applied during CHA processing have a significant influence on their infection resistance,” said Dr. Viola Steffen of Hannover (Germany) Medical School and her colleagues. The average storage time of CHAs was 8.5 years, with the longest having been stored for 10 years.

The study involved microbiologic tests in vitro of three different antibiotic regimens used in processing CHA: gentamicin-piperacillin-vancomycin-metronidazole-amphotericin B (group A); gentamicin-piperacillin-flucloxacillin-metronidazole-amphotericin B (group B); and meropenem-vancomycin-tobramycin-colistin-amphotericin B (group C). The combinations are used to counteract Staphylococcus epidermidis and Staphylococcus aureus.

The study exposed pieces of 10 CHAs to different microbes and determined that regimen groups B and C were more effective than group A in eradicating gram-positive organisms. Specifically, group C was most resistant to Escherichia coli, whereas group B was most effective against Pseudomonas aeruginosa. Aortic tissue showed significantly less contamination with staphylococcal bacteria than valve grafts, the study reported.

Dr. Steffen and her colleagues said that tissue banks use antibiotic protocols during CHA processing, but they differ substantially. “Our results support the hypothesis that infection resistance of CHAs depends on the antibiotic pretreatment during processing and their residual activity,” they said.

The study had four key findings:

• The infection resistance of aortic wall and valve tissue differed significantly.

• In aortic wall specimens, group A specimens exhibited increased adherence of S. epidermidis, with vancomycin in group A and flucloxacillin in group B being the only differentiating agents between the two.

• Cryopreserved aortic vessels had a propensity toward reduced infection resistance against P. aeruginosa.

• Morphologic changes occurred in the microorganisms, especially rod-shaped E. coli, indicating that regional antibiotic release alters bacterial growth without eliminating all adherent bacteria.

Dr. Steffen and her colleagues noted that while previous studies determined that residual concentrations of antibiotics used in processing CHA heart valves and blood vessels are still present after they are prepared for implantation, they neither measured the antibacterial affect, clarified the period of cryopreservation nor differentiated between valve and vessel tissue (PLoS One. 2014;9:e112679; Transfus Med Hemother. 2011;38:379-86).

The Hannover researchers found that only a few gram-positive microorganisms adhered to aortic wall specimens, although they found “extensive adherence” of S. epidermidis in group A specimens. Valves, however, “were completely colonized” with both strains of staphylococcal bacteria, although the severity of contamination varied depending on the regimen used.

The findings raise some questions about the antibiotic properties of CHAs. “Because their infection resistance depends on the antibiotic combination selected during processing, further investigations concerning this treatment are necessary to improve the antimicrobial activity against frequent and highly virulent infection-causing bacteria,” Dr. Steffen and her colleagues said.

Dr. Steffen and her coauthors had no financial relationships to disclose.