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Hospitalists target inpatient glycemic control
SHM benchmarks provide ‘objective format’ for improving outcomes
Physicians are trained to manage their patients’ diabetes and often do a meticulous job – one on one. But in order to maximize glycemic control outcomes throughout the hospital, you need a kind of diabetic epidemiology team to focus on the data, said Andjela Drincic, MD, an endocrinologist at Nebraska Medicine, the clinical partner of the University of Nebraska Medical Center in Omaha.
As medical director for diabetes stewardship, Dr. Drincic serves as the epidemiologic lead for her hospital, which has worked systematically to improve inpatient glycemic control since 2012 – with help from the Society of Hospital Medicine.
“You need a team and to set up a system that works, with protocols and some way of knowing if the protocols are succeeding,” Dr. Drincic said. “Quality improvement targets are never static.” She credited SHM’s glycemic control eQUIPS (Electronic Quality Improvement Program), an online quality improvement resource and collaborative of 104 participating hospitals, for providing the support and the data needed to drive glycemic QI efforts at Nebraska Medicine. SHM provided reporting metrics, quarterly benchmarking reports, a library of tools and resources, an implementation guide, educational webinars on demand and, for some participants, mentored implementation with the advice of a leading expert in the field.
One big reason for giving more attention to glycemic control in the hospital is patient safety, said Gregory Maynard, MD, MHM, clinical professor and chief quality officer at the University of California–Davis Medical Center and SHM’s project team leader for eQUIPS.
“Hyperglycemia in hospitalized patients is an extraordinarily common and growing problem, affecting up to 40%-50% of patients in the hospital,” he said. In 2012, 7.7 million hospital stays involved patients with diabetes, the seventh leading cause of death in the United States.1
Hyperglycemia is linked to elevated rates of medical complications, infections, wound complications, hospital mortality, length of stay, readmissions, and ICU admissions, along with other outcomes not directly related to diabetes. Hyperglycemia in hospitalized patients who have not been given a diagnosis of diabetes is, if anything, more dangerous. Add the related risk for hypoglycemia, and clinicians are challenged to keep their patients controlled within the zone between the extremes of hyper- and hypoglycemia. The American Diabetes Association recently issued recommendations with more relaxed glucose targets between 140 and 180 mg/dL for most patients in non–intensive care settings.2
“To not have a standardized way of managing hyperglycemia for your hospital seems like an enormous missed opportunity,” Dr. Maynard said. “If someone comes into the hospital with a chronic condition of diabetes that you ignore, just maintaining them in the hospital and sending them back out into the world without addressing the underlying condition is not good care. You have missed an important opportunity to alter the course of a serious chronic condition.”
Dr. Maynard said SHM recognized this opportunity when it established eQUIPS. “Hospitalists are often tasked with taking care of patients with glycemic issues because there may not be an endocrinologist readily accessible in the hospital,” he said. “We have seen through our benchmarking in eQUIPS incredible variability – with 10-fold differences in hyperglycemia and hypoglycemia rates between the best- and worst-performing sites. The biggest variable is whether the hospital systematically manages glycemic control. We have also shown that achieving high levels of glycemic control and low hypoglycemia rates concurrently is very possible.”
Reliable benchmarks
Nebraska Medicine enrolled in eQUIPS in 2012.
“We utilize SHM’s glucometrics (standardized analyses of inpatient glycemic control data).”3 said Dr. Drincic. “I was looking for a reliable glucometric system and some way to make comparisons with other hospitals when I came across the data Dr. Maynard published about SHM via a PubMed search. We needed outcomes that are validated in the literature and comparison groups.”
Nebraska Medicine has also received a certificate of distinction for inpatient diabetes care from the Joint Commission, and Dr. Drincic is active in PRIDE (Planning Research in Inpatient Diabetes), a national consortium of leading investigators in inpatient diabetes care formed to promote collaborative research. The PRIDE group meets yearly at the ADA conference, communicates regularly by email, and publishes articles.
“Once a year I present our glycemic control data to our administration and to the quality and safety committees at the hospital. I have been pleased with the level of support we have received,” Dr. Drincic said. “We needed a mandate to do this, but when I reported the impact on readmissions and other outcomes, I got the full support of administration. This would have been a lot harder without SHM.”
Engagement with hospitalists is another key to the glucose management project’s success, Dr. Drincic said. “We as endocrinologists think we know how to manage diabetes, but hospitalists have the daunting task of dealing with all of the patient’s medical issues. If we don’t have a strong collaboration, how can we change practice hospitalwide?” Rachel Thompson, MD, SFHM, Nebraska Medicine’s chief of hospital medicine, participates in the glucose management project, Dr. Drincic said.
“We occasionally are guests at hospitalist meetings to share new glucose treatment algorithms,” she said. “We’re also looking at collaborating on other quality initiatives, for example, studying how perioperative dexamethasone affects glycemic control. We built this relationship with hospitalists by establishing trust while trying to shed a reputation as ‘sugar police.’ I don’t want hospitalists saying ‘There she goes again’ whenever I come on the unit. We have tried to establish personal relationships and figure out what the hospitalists need, especially relative to EPIC (the hospital’s electronic medical record software).”
Dr. Thompson said her group’s recent growth to nearly 70 clinicians has increased its footprint hospitalwide and given hospitalists a greater opportunity to influence glycemic control. “We see up to a third of the patients in the hospital outside of the ICU. Glycemic control is something you learn as a hospitalist – It’s a very important frontline quality issue. In the patient list on EPIC every morning we have a field highlighting all patients with glycemic control issues,” she said.
“Poor glucose control is associated with poor outcomes for our patients. We need the right systems in place for patient safety. Moreover, if we are ignoring glycemic control when the patient is in the hospital, we’re sending the wrong message and setting a bad example for our patients when they return home.”
Lack of clear metrics
A significant defect in the infrastructure of many glucose management programs is the lack of clear metrics for outcomes, Dr. Maynard said. Nearly one-third of hospitals in the United States have no standardized metric to track the quality of their inpatient glycemic management, a sobering statistic considering that the first step in any QI initiative is to define and measure the problem at hand.
“I believe the main reason that glycemic control has been left off hospitals’ radar screens is that we still have not adopted national, publicly reported quality measures for glycemic control, although those were proposed recently by a government interagency work group,” Dr. Maynard said. “Until that happens, we’ll continue to see uneven response.”
The first step for frontline hospitalists is to learn and understand the basics of glucose control, for example, basal bolus insulin administration, and to stop writing orders for sliding scale insulin as the sole means of controlling hyperglycemia.
“Develop and adopt standards of practice for insulin administration in your hospital,” Dr. Maynard said. “Be part of the solution, not the problem. Once you get into the weeds – patients on steroids or on total parenteral nutrition – it can get tricky. But it’s important to get the basics right and move beyond inertia on this topic.”
The glycemic team at Nebraska Medicine includes, in addition to Dr. Drincic and Dr. Thompson, an endocrinology fellow, diabetes case managers, resource nurses, nurse leadership, pharmacists, inpatient care transitions coordinators, and representatives from pediatrics and critical care, all working to impact the overall quality of glycemic management in the hospital. Jon Knezevich, PharmD is diabetes stewardship pharmacy coordinator, and Shelly Lautenbaugh, RN, CDE, is diabetes lead care manager and diabetes coordinator for the Joint Commission certificate program. Diabetes stewardship also includes online and live training courses and a class in acute glucose management for the diabetes resource nurses, who bring the knowledge back to their units.
The glucose team’s job is to make sure patients are cared for safely, using appropriate policies and procedures, education, and training, Ms. Lautenbaugh said. “We have a mission as a hospital to transform people’s lives. We try to live our values, and everything follows from the focus on patient safety,” she added. “If our patients can receive extraordinary care and leave better informed about their condition than when they came in, and then we don’t see them again, we’ve achieved our ultimate goal.”
Hyperglycemia is most often not the primary reason why patients are hospitalized, Ms. Lautenbaugh said. “But we need to give them appropriate glucose management regardless. We’ve worked with bedside staff, nurse leadership, and teams to develop plans to raise our outcome scores. We have a lot of different outcomes we examine, and it’s always evolving.”
Quality metrics are incorporated into the electronic medical record, but those reports are not timely enough for day-to-day management, Dr. Knezevich said. “So we created a diabetes dashboard, constantly updated in real time to identify patients who are out of glycemic control.” The measures tracked include a mean patient day glucose score, percentage of readings within recommended limits, mean time between measured low readings and next documented reading or resolution of hypoglycemia, readmission rates, and diabetes nutrition assessments.
For hospitals with diabetes certificates, the Joint Commission also requires that every patient with hyperglycemia receives a clinic visit 30 days after discharge to make sure they are receiving appropriate follow-up care. Other facets of the Nebraska glycemic initiative include utilizing the hospital’s voluntary “Meds to Beds” program, which brings prescribed medications to the patient’s room at discharge. “We offer a diabetes discharge kit for patients who are self-pay, with all of the insulin and medical supplies they will need to get to the 30-day follow-up visit,” Dr. Knezevich said. “We can dream up amazing treatment regimens, but if they can’t afford the medications, what have we accomplished?”
SHM’s external benchmarks have provided an objective format for comparing and improving outcomes, Ms. Lautenbaugh said. “We like to see where we are and use the data to make significant improvements, but we’re also focused on internal assessments. If we make changes for a given metric, how does it affect performance in other areas?” One important metric is percentage of glucose readings within target range hospitalwide. “Our overall goal is 75%. It was 72% in April 2018, and we’ve raised it to 74.4%. It’s a small gain but it shows steady progress. Little steps make small but steady improvement,” she said.
“One area where we were not pleased was the occurrence of hypoglycemia,” Ms. Lautenbaugh said. “We did a root cause analysis of every hypoglycemic event, including several reports for patients who didn’t have diabetes at all. We had to weed out some that weren’t pertinent to our quality questions, but for those that are, the diabetes case manager calls the provider to make sure they were aware of the incident. We were able to identify the outliers in noncritical care, which we’re now able to tackle using a systematic approach.”
Get on the bus
Hospitalists are also integrally involved in a hospital glycemic improvement initiative at Orange Regional Medical Center (ORMC) in Middletown, N.Y.
The Glycemic Improvement Team (GIT) was formed in 2012 when a new hospital campus opened and EPIC was implemented as the hospital’s EMR. But glycemic control has taken on greater focus since 2015, when ORMC enrolled in eQUIPS, said Lorraine Porcaro, RN, the hospital’s diabetes clinical manager. The glycemic control team includes representatives from medicine, nursing, case management, laboratory, nutrition, pharmacy, wound care, and quality improvement.
Implementing the new EMR offered the opportunity to track a number of medical values in real time, Ms. Porcaro said. ORMC has focused its glycemic quality improvement efforts on hypoglycemia and hyperglycemia, with a recent emphasis on the need for improvements related to glucose reassessment 15 minutes post hypoglycemia treatment. More than a hundred “Diabetes Champions” have completed 16 hours of advanced training in diabetes and provide in-unit mentorship for other staff.
The ORMC team’s glycemic improvement “bus” is a rolling cart that goes from unit to unit supplying nurse education, reminders, copies of department-specific policies and protocols, and treats for staff. “It’s what we’re known for,” Ms. Porcaro said. Pens with the motto: “Don’t Miss the Bus! Retest in 15!” summarize the GIT’s current focus on post–hypoglycemia treatment retesting.
Hospitalists were part of the glycemic improvement process at ORMC from the beginning and are still involved, said Adrian Paraschiv, MD, FHM, a hospitalist and assistant director of the medical center, as well as the ORMC director of clinical information technology. ORMC initiated hospitalist coverage in 1998 and now has three HM groups, two of them represented on the glycemic improvement team.
“Like any hospital, we feel we should minimize hypoglycemic events,” Dr. Paraschiv explained. “This became important for other hospital departments, and we recognized we needed a major QI initiative to improve our outcomes hospitalwide. In the process, we noticed what other people were saying: Results from improving glycemic control included reduced length of stay, cost, and infections. That provided motivation for the hospital to support our initiative.”
Glucose management isn’t only about blood sugar, but whether the patient ate or not, their other blood work, the level of education for patient and staff, and a variety of other inputs, Dr. Paraschiv said. “All of these things were in the EMR but all over the place. EPIC had an incipient structure for pulling the data together, and we modified it to show everything that’s going on with the patient’s glycemic control on a single screen. We can build order sets and issue different reports.”
Today at ORMC, hypoglycemia is reassessed within 30 minutes more than 50% of the time. “It will never be at 100%, but we wanted to at least be at the national mean for eQUIPS hospitals. Our stretch goal was to be in the top quartile, and by the end of 2017, we realized that goal,” Ms. Porcaro said. Sometimes, because of changes in patients and staff, the GIT needs to repeat the education and review policies. “Since then, it’s been a matter of continuing staff education; sharing glucose data with stakeholders; talking about goals for ICU and non-ICU units; and, when needed, rolling out the bus.”
Participation in eQUIPS has made it possible to gather this information in one place and present it in a way that makes sense to physicians, Dr. Paraschiv said. “Dr. Maynard and SHM showed us how to put the data together to add value. Using these tools, we started looking at our processes, what needed to change, and what we are able to change. Now we’re examining what happens afterward. Can we use the electronic system to automatically alert physicians to make changes to the treatment regimen in real time? We continue to improve using upgrades to our EMR, such as an alert system with best practice advisories for the clinician. We now think we can actually achieve what we set out to achieve,” he said.
“Our idea was that we needed to market this program throughout the hospital – starting from the kitchen, meal delivery staff, IT, laboratory, medical and nursing staff,” Ms. Porcaro said. “The issue is multifactorial – it’s for the entire hospital. My heart is warmed when I see the woman who delivers the meals asking the patient: ‘Have you gotten your insulin shot?’ ”
References
1. Corvino L et al. “Management of diabetes and hyperglycemia in hospitalized patients.” Updated 2017 Oct 1 in De Groot LJ et al. editors. Endotext. South Dartmouth (MA): MDText.com 2000.
2. American Diabetes Association. Glycemic targets. Diabetes Care 2017 Jan;40(Suppl 1):S48-56.
3. Maynard G et al. “Design and implementation of a web-based reporting and benchmarking center for inpatient glucometrics.” J Diabetes Sci Technol. 2014 May 12;8(4):630-40.
SHM benchmarks provide ‘objective format’ for improving outcomes
SHM benchmarks provide ‘objective format’ for improving outcomes
Physicians are trained to manage their patients’ diabetes and often do a meticulous job – one on one. But in order to maximize glycemic control outcomes throughout the hospital, you need a kind of diabetic epidemiology team to focus on the data, said Andjela Drincic, MD, an endocrinologist at Nebraska Medicine, the clinical partner of the University of Nebraska Medical Center in Omaha.
As medical director for diabetes stewardship, Dr. Drincic serves as the epidemiologic lead for her hospital, which has worked systematically to improve inpatient glycemic control since 2012 – with help from the Society of Hospital Medicine.
“You need a team and to set up a system that works, with protocols and some way of knowing if the protocols are succeeding,” Dr. Drincic said. “Quality improvement targets are never static.” She credited SHM’s glycemic control eQUIPS (Electronic Quality Improvement Program), an online quality improvement resource and collaborative of 104 participating hospitals, for providing the support and the data needed to drive glycemic QI efforts at Nebraska Medicine. SHM provided reporting metrics, quarterly benchmarking reports, a library of tools and resources, an implementation guide, educational webinars on demand and, for some participants, mentored implementation with the advice of a leading expert in the field.
One big reason for giving more attention to glycemic control in the hospital is patient safety, said Gregory Maynard, MD, MHM, clinical professor and chief quality officer at the University of California–Davis Medical Center and SHM’s project team leader for eQUIPS.
“Hyperglycemia in hospitalized patients is an extraordinarily common and growing problem, affecting up to 40%-50% of patients in the hospital,” he said. In 2012, 7.7 million hospital stays involved patients with diabetes, the seventh leading cause of death in the United States.1
Hyperglycemia is linked to elevated rates of medical complications, infections, wound complications, hospital mortality, length of stay, readmissions, and ICU admissions, along with other outcomes not directly related to diabetes. Hyperglycemia in hospitalized patients who have not been given a diagnosis of diabetes is, if anything, more dangerous. Add the related risk for hypoglycemia, and clinicians are challenged to keep their patients controlled within the zone between the extremes of hyper- and hypoglycemia. The American Diabetes Association recently issued recommendations with more relaxed glucose targets between 140 and 180 mg/dL for most patients in non–intensive care settings.2
“To not have a standardized way of managing hyperglycemia for your hospital seems like an enormous missed opportunity,” Dr. Maynard said. “If someone comes into the hospital with a chronic condition of diabetes that you ignore, just maintaining them in the hospital and sending them back out into the world without addressing the underlying condition is not good care. You have missed an important opportunity to alter the course of a serious chronic condition.”
Dr. Maynard said SHM recognized this opportunity when it established eQUIPS. “Hospitalists are often tasked with taking care of patients with glycemic issues because there may not be an endocrinologist readily accessible in the hospital,” he said. “We have seen through our benchmarking in eQUIPS incredible variability – with 10-fold differences in hyperglycemia and hypoglycemia rates between the best- and worst-performing sites. The biggest variable is whether the hospital systematically manages glycemic control. We have also shown that achieving high levels of glycemic control and low hypoglycemia rates concurrently is very possible.”
Reliable benchmarks
Nebraska Medicine enrolled in eQUIPS in 2012.
“We utilize SHM’s glucometrics (standardized analyses of inpatient glycemic control data).”3 said Dr. Drincic. “I was looking for a reliable glucometric system and some way to make comparisons with other hospitals when I came across the data Dr. Maynard published about SHM via a PubMed search. We needed outcomes that are validated in the literature and comparison groups.”
Nebraska Medicine has also received a certificate of distinction for inpatient diabetes care from the Joint Commission, and Dr. Drincic is active in PRIDE (Planning Research in Inpatient Diabetes), a national consortium of leading investigators in inpatient diabetes care formed to promote collaborative research. The PRIDE group meets yearly at the ADA conference, communicates regularly by email, and publishes articles.
“Once a year I present our glycemic control data to our administration and to the quality and safety committees at the hospital. I have been pleased with the level of support we have received,” Dr. Drincic said. “We needed a mandate to do this, but when I reported the impact on readmissions and other outcomes, I got the full support of administration. This would have been a lot harder without SHM.”
Engagement with hospitalists is another key to the glucose management project’s success, Dr. Drincic said. “We as endocrinologists think we know how to manage diabetes, but hospitalists have the daunting task of dealing with all of the patient’s medical issues. If we don’t have a strong collaboration, how can we change practice hospitalwide?” Rachel Thompson, MD, SFHM, Nebraska Medicine’s chief of hospital medicine, participates in the glucose management project, Dr. Drincic said.
“We occasionally are guests at hospitalist meetings to share new glucose treatment algorithms,” she said. “We’re also looking at collaborating on other quality initiatives, for example, studying how perioperative dexamethasone affects glycemic control. We built this relationship with hospitalists by establishing trust while trying to shed a reputation as ‘sugar police.’ I don’t want hospitalists saying ‘There she goes again’ whenever I come on the unit. We have tried to establish personal relationships and figure out what the hospitalists need, especially relative to EPIC (the hospital’s electronic medical record software).”
Dr. Thompson said her group’s recent growth to nearly 70 clinicians has increased its footprint hospitalwide and given hospitalists a greater opportunity to influence glycemic control. “We see up to a third of the patients in the hospital outside of the ICU. Glycemic control is something you learn as a hospitalist – It’s a very important frontline quality issue. In the patient list on EPIC every morning we have a field highlighting all patients with glycemic control issues,” she said.
“Poor glucose control is associated with poor outcomes for our patients. We need the right systems in place for patient safety. Moreover, if we are ignoring glycemic control when the patient is in the hospital, we’re sending the wrong message and setting a bad example for our patients when they return home.”
Lack of clear metrics
A significant defect in the infrastructure of many glucose management programs is the lack of clear metrics for outcomes, Dr. Maynard said. Nearly one-third of hospitals in the United States have no standardized metric to track the quality of their inpatient glycemic management, a sobering statistic considering that the first step in any QI initiative is to define and measure the problem at hand.
“I believe the main reason that glycemic control has been left off hospitals’ radar screens is that we still have not adopted national, publicly reported quality measures for glycemic control, although those were proposed recently by a government interagency work group,” Dr. Maynard said. “Until that happens, we’ll continue to see uneven response.”
The first step for frontline hospitalists is to learn and understand the basics of glucose control, for example, basal bolus insulin administration, and to stop writing orders for sliding scale insulin as the sole means of controlling hyperglycemia.
“Develop and adopt standards of practice for insulin administration in your hospital,” Dr. Maynard said. “Be part of the solution, not the problem. Once you get into the weeds – patients on steroids or on total parenteral nutrition – it can get tricky. But it’s important to get the basics right and move beyond inertia on this topic.”
The glycemic team at Nebraska Medicine includes, in addition to Dr. Drincic and Dr. Thompson, an endocrinology fellow, diabetes case managers, resource nurses, nurse leadership, pharmacists, inpatient care transitions coordinators, and representatives from pediatrics and critical care, all working to impact the overall quality of glycemic management in the hospital. Jon Knezevich, PharmD is diabetes stewardship pharmacy coordinator, and Shelly Lautenbaugh, RN, CDE, is diabetes lead care manager and diabetes coordinator for the Joint Commission certificate program. Diabetes stewardship also includes online and live training courses and a class in acute glucose management for the diabetes resource nurses, who bring the knowledge back to their units.
The glucose team’s job is to make sure patients are cared for safely, using appropriate policies and procedures, education, and training, Ms. Lautenbaugh said. “We have a mission as a hospital to transform people’s lives. We try to live our values, and everything follows from the focus on patient safety,” she added. “If our patients can receive extraordinary care and leave better informed about their condition than when they came in, and then we don’t see them again, we’ve achieved our ultimate goal.”
Hyperglycemia is most often not the primary reason why patients are hospitalized, Ms. Lautenbaugh said. “But we need to give them appropriate glucose management regardless. We’ve worked with bedside staff, nurse leadership, and teams to develop plans to raise our outcome scores. We have a lot of different outcomes we examine, and it’s always evolving.”
Quality metrics are incorporated into the electronic medical record, but those reports are not timely enough for day-to-day management, Dr. Knezevich said. “So we created a diabetes dashboard, constantly updated in real time to identify patients who are out of glycemic control.” The measures tracked include a mean patient day glucose score, percentage of readings within recommended limits, mean time between measured low readings and next documented reading or resolution of hypoglycemia, readmission rates, and diabetes nutrition assessments.
For hospitals with diabetes certificates, the Joint Commission also requires that every patient with hyperglycemia receives a clinic visit 30 days after discharge to make sure they are receiving appropriate follow-up care. Other facets of the Nebraska glycemic initiative include utilizing the hospital’s voluntary “Meds to Beds” program, which brings prescribed medications to the patient’s room at discharge. “We offer a diabetes discharge kit for patients who are self-pay, with all of the insulin and medical supplies they will need to get to the 30-day follow-up visit,” Dr. Knezevich said. “We can dream up amazing treatment regimens, but if they can’t afford the medications, what have we accomplished?”
SHM’s external benchmarks have provided an objective format for comparing and improving outcomes, Ms. Lautenbaugh said. “We like to see where we are and use the data to make significant improvements, but we’re also focused on internal assessments. If we make changes for a given metric, how does it affect performance in other areas?” One important metric is percentage of glucose readings within target range hospitalwide. “Our overall goal is 75%. It was 72% in April 2018, and we’ve raised it to 74.4%. It’s a small gain but it shows steady progress. Little steps make small but steady improvement,” she said.
“One area where we were not pleased was the occurrence of hypoglycemia,” Ms. Lautenbaugh said. “We did a root cause analysis of every hypoglycemic event, including several reports for patients who didn’t have diabetes at all. We had to weed out some that weren’t pertinent to our quality questions, but for those that are, the diabetes case manager calls the provider to make sure they were aware of the incident. We were able to identify the outliers in noncritical care, which we’re now able to tackle using a systematic approach.”
Get on the bus
Hospitalists are also integrally involved in a hospital glycemic improvement initiative at Orange Regional Medical Center (ORMC) in Middletown, N.Y.
The Glycemic Improvement Team (GIT) was formed in 2012 when a new hospital campus opened and EPIC was implemented as the hospital’s EMR. But glycemic control has taken on greater focus since 2015, when ORMC enrolled in eQUIPS, said Lorraine Porcaro, RN, the hospital’s diabetes clinical manager. The glycemic control team includes representatives from medicine, nursing, case management, laboratory, nutrition, pharmacy, wound care, and quality improvement.
Implementing the new EMR offered the opportunity to track a number of medical values in real time, Ms. Porcaro said. ORMC has focused its glycemic quality improvement efforts on hypoglycemia and hyperglycemia, with a recent emphasis on the need for improvements related to glucose reassessment 15 minutes post hypoglycemia treatment. More than a hundred “Diabetes Champions” have completed 16 hours of advanced training in diabetes and provide in-unit mentorship for other staff.
The ORMC team’s glycemic improvement “bus” is a rolling cart that goes from unit to unit supplying nurse education, reminders, copies of department-specific policies and protocols, and treats for staff. “It’s what we’re known for,” Ms. Porcaro said. Pens with the motto: “Don’t Miss the Bus! Retest in 15!” summarize the GIT’s current focus on post–hypoglycemia treatment retesting.
Hospitalists were part of the glycemic improvement process at ORMC from the beginning and are still involved, said Adrian Paraschiv, MD, FHM, a hospitalist and assistant director of the medical center, as well as the ORMC director of clinical information technology. ORMC initiated hospitalist coverage in 1998 and now has three HM groups, two of them represented on the glycemic improvement team.
“Like any hospital, we feel we should minimize hypoglycemic events,” Dr. Paraschiv explained. “This became important for other hospital departments, and we recognized we needed a major QI initiative to improve our outcomes hospitalwide. In the process, we noticed what other people were saying: Results from improving glycemic control included reduced length of stay, cost, and infections. That provided motivation for the hospital to support our initiative.”
Glucose management isn’t only about blood sugar, but whether the patient ate or not, their other blood work, the level of education for patient and staff, and a variety of other inputs, Dr. Paraschiv said. “All of these things were in the EMR but all over the place. EPIC had an incipient structure for pulling the data together, and we modified it to show everything that’s going on with the patient’s glycemic control on a single screen. We can build order sets and issue different reports.”
Today at ORMC, hypoglycemia is reassessed within 30 minutes more than 50% of the time. “It will never be at 100%, but we wanted to at least be at the national mean for eQUIPS hospitals. Our stretch goal was to be in the top quartile, and by the end of 2017, we realized that goal,” Ms. Porcaro said. Sometimes, because of changes in patients and staff, the GIT needs to repeat the education and review policies. “Since then, it’s been a matter of continuing staff education; sharing glucose data with stakeholders; talking about goals for ICU and non-ICU units; and, when needed, rolling out the bus.”
Participation in eQUIPS has made it possible to gather this information in one place and present it in a way that makes sense to physicians, Dr. Paraschiv said. “Dr. Maynard and SHM showed us how to put the data together to add value. Using these tools, we started looking at our processes, what needed to change, and what we are able to change. Now we’re examining what happens afterward. Can we use the electronic system to automatically alert physicians to make changes to the treatment regimen in real time? We continue to improve using upgrades to our EMR, such as an alert system with best practice advisories for the clinician. We now think we can actually achieve what we set out to achieve,” he said.
“Our idea was that we needed to market this program throughout the hospital – starting from the kitchen, meal delivery staff, IT, laboratory, medical and nursing staff,” Ms. Porcaro said. “The issue is multifactorial – it’s for the entire hospital. My heart is warmed when I see the woman who delivers the meals asking the patient: ‘Have you gotten your insulin shot?’ ”
References
1. Corvino L et al. “Management of diabetes and hyperglycemia in hospitalized patients.” Updated 2017 Oct 1 in De Groot LJ et al. editors. Endotext. South Dartmouth (MA): MDText.com 2000.
2. American Diabetes Association. Glycemic targets. Diabetes Care 2017 Jan;40(Suppl 1):S48-56.
3. Maynard G et al. “Design and implementation of a web-based reporting and benchmarking center for inpatient glucometrics.” J Diabetes Sci Technol. 2014 May 12;8(4):630-40.
Physicians are trained to manage their patients’ diabetes and often do a meticulous job – one on one. But in order to maximize glycemic control outcomes throughout the hospital, you need a kind of diabetic epidemiology team to focus on the data, said Andjela Drincic, MD, an endocrinologist at Nebraska Medicine, the clinical partner of the University of Nebraska Medical Center in Omaha.
As medical director for diabetes stewardship, Dr. Drincic serves as the epidemiologic lead for her hospital, which has worked systematically to improve inpatient glycemic control since 2012 – with help from the Society of Hospital Medicine.
“You need a team and to set up a system that works, with protocols and some way of knowing if the protocols are succeeding,” Dr. Drincic said. “Quality improvement targets are never static.” She credited SHM’s glycemic control eQUIPS (Electronic Quality Improvement Program), an online quality improvement resource and collaborative of 104 participating hospitals, for providing the support and the data needed to drive glycemic QI efforts at Nebraska Medicine. SHM provided reporting metrics, quarterly benchmarking reports, a library of tools and resources, an implementation guide, educational webinars on demand and, for some participants, mentored implementation with the advice of a leading expert in the field.
One big reason for giving more attention to glycemic control in the hospital is patient safety, said Gregory Maynard, MD, MHM, clinical professor and chief quality officer at the University of California–Davis Medical Center and SHM’s project team leader for eQUIPS.
“Hyperglycemia in hospitalized patients is an extraordinarily common and growing problem, affecting up to 40%-50% of patients in the hospital,” he said. In 2012, 7.7 million hospital stays involved patients with diabetes, the seventh leading cause of death in the United States.1
Hyperglycemia is linked to elevated rates of medical complications, infections, wound complications, hospital mortality, length of stay, readmissions, and ICU admissions, along with other outcomes not directly related to diabetes. Hyperglycemia in hospitalized patients who have not been given a diagnosis of diabetes is, if anything, more dangerous. Add the related risk for hypoglycemia, and clinicians are challenged to keep their patients controlled within the zone between the extremes of hyper- and hypoglycemia. The American Diabetes Association recently issued recommendations with more relaxed glucose targets between 140 and 180 mg/dL for most patients in non–intensive care settings.2
“To not have a standardized way of managing hyperglycemia for your hospital seems like an enormous missed opportunity,” Dr. Maynard said. “If someone comes into the hospital with a chronic condition of diabetes that you ignore, just maintaining them in the hospital and sending them back out into the world without addressing the underlying condition is not good care. You have missed an important opportunity to alter the course of a serious chronic condition.”
Dr. Maynard said SHM recognized this opportunity when it established eQUIPS. “Hospitalists are often tasked with taking care of patients with glycemic issues because there may not be an endocrinologist readily accessible in the hospital,” he said. “We have seen through our benchmarking in eQUIPS incredible variability – with 10-fold differences in hyperglycemia and hypoglycemia rates between the best- and worst-performing sites. The biggest variable is whether the hospital systematically manages glycemic control. We have also shown that achieving high levels of glycemic control and low hypoglycemia rates concurrently is very possible.”
Reliable benchmarks
Nebraska Medicine enrolled in eQUIPS in 2012.
“We utilize SHM’s glucometrics (standardized analyses of inpatient glycemic control data).”3 said Dr. Drincic. “I was looking for a reliable glucometric system and some way to make comparisons with other hospitals when I came across the data Dr. Maynard published about SHM via a PubMed search. We needed outcomes that are validated in the literature and comparison groups.”
Nebraska Medicine has also received a certificate of distinction for inpatient diabetes care from the Joint Commission, and Dr. Drincic is active in PRIDE (Planning Research in Inpatient Diabetes), a national consortium of leading investigators in inpatient diabetes care formed to promote collaborative research. The PRIDE group meets yearly at the ADA conference, communicates regularly by email, and publishes articles.
“Once a year I present our glycemic control data to our administration and to the quality and safety committees at the hospital. I have been pleased with the level of support we have received,” Dr. Drincic said. “We needed a mandate to do this, but when I reported the impact on readmissions and other outcomes, I got the full support of administration. This would have been a lot harder without SHM.”
Engagement with hospitalists is another key to the glucose management project’s success, Dr. Drincic said. “We as endocrinologists think we know how to manage diabetes, but hospitalists have the daunting task of dealing with all of the patient’s medical issues. If we don’t have a strong collaboration, how can we change practice hospitalwide?” Rachel Thompson, MD, SFHM, Nebraska Medicine’s chief of hospital medicine, participates in the glucose management project, Dr. Drincic said.
“We occasionally are guests at hospitalist meetings to share new glucose treatment algorithms,” she said. “We’re also looking at collaborating on other quality initiatives, for example, studying how perioperative dexamethasone affects glycemic control. We built this relationship with hospitalists by establishing trust while trying to shed a reputation as ‘sugar police.’ I don’t want hospitalists saying ‘There she goes again’ whenever I come on the unit. We have tried to establish personal relationships and figure out what the hospitalists need, especially relative to EPIC (the hospital’s electronic medical record software).”
Dr. Thompson said her group’s recent growth to nearly 70 clinicians has increased its footprint hospitalwide and given hospitalists a greater opportunity to influence glycemic control. “We see up to a third of the patients in the hospital outside of the ICU. Glycemic control is something you learn as a hospitalist – It’s a very important frontline quality issue. In the patient list on EPIC every morning we have a field highlighting all patients with glycemic control issues,” she said.
“Poor glucose control is associated with poor outcomes for our patients. We need the right systems in place for patient safety. Moreover, if we are ignoring glycemic control when the patient is in the hospital, we’re sending the wrong message and setting a bad example for our patients when they return home.”
Lack of clear metrics
A significant defect in the infrastructure of many glucose management programs is the lack of clear metrics for outcomes, Dr. Maynard said. Nearly one-third of hospitals in the United States have no standardized metric to track the quality of their inpatient glycemic management, a sobering statistic considering that the first step in any QI initiative is to define and measure the problem at hand.
“I believe the main reason that glycemic control has been left off hospitals’ radar screens is that we still have not adopted national, publicly reported quality measures for glycemic control, although those were proposed recently by a government interagency work group,” Dr. Maynard said. “Until that happens, we’ll continue to see uneven response.”
The first step for frontline hospitalists is to learn and understand the basics of glucose control, for example, basal bolus insulin administration, and to stop writing orders for sliding scale insulin as the sole means of controlling hyperglycemia.
“Develop and adopt standards of practice for insulin administration in your hospital,” Dr. Maynard said. “Be part of the solution, not the problem. Once you get into the weeds – patients on steroids or on total parenteral nutrition – it can get tricky. But it’s important to get the basics right and move beyond inertia on this topic.”
The glycemic team at Nebraska Medicine includes, in addition to Dr. Drincic and Dr. Thompson, an endocrinology fellow, diabetes case managers, resource nurses, nurse leadership, pharmacists, inpatient care transitions coordinators, and representatives from pediatrics and critical care, all working to impact the overall quality of glycemic management in the hospital. Jon Knezevich, PharmD is diabetes stewardship pharmacy coordinator, and Shelly Lautenbaugh, RN, CDE, is diabetes lead care manager and diabetes coordinator for the Joint Commission certificate program. Diabetes stewardship also includes online and live training courses and a class in acute glucose management for the diabetes resource nurses, who bring the knowledge back to their units.
The glucose team’s job is to make sure patients are cared for safely, using appropriate policies and procedures, education, and training, Ms. Lautenbaugh said. “We have a mission as a hospital to transform people’s lives. We try to live our values, and everything follows from the focus on patient safety,” she added. “If our patients can receive extraordinary care and leave better informed about their condition than when they came in, and then we don’t see them again, we’ve achieved our ultimate goal.”
Hyperglycemia is most often not the primary reason why patients are hospitalized, Ms. Lautenbaugh said. “But we need to give them appropriate glucose management regardless. We’ve worked with bedside staff, nurse leadership, and teams to develop plans to raise our outcome scores. We have a lot of different outcomes we examine, and it’s always evolving.”
Quality metrics are incorporated into the electronic medical record, but those reports are not timely enough for day-to-day management, Dr. Knezevich said. “So we created a diabetes dashboard, constantly updated in real time to identify patients who are out of glycemic control.” The measures tracked include a mean patient day glucose score, percentage of readings within recommended limits, mean time between measured low readings and next documented reading or resolution of hypoglycemia, readmission rates, and diabetes nutrition assessments.
For hospitals with diabetes certificates, the Joint Commission also requires that every patient with hyperglycemia receives a clinic visit 30 days after discharge to make sure they are receiving appropriate follow-up care. Other facets of the Nebraska glycemic initiative include utilizing the hospital’s voluntary “Meds to Beds” program, which brings prescribed medications to the patient’s room at discharge. “We offer a diabetes discharge kit for patients who are self-pay, with all of the insulin and medical supplies they will need to get to the 30-day follow-up visit,” Dr. Knezevich said. “We can dream up amazing treatment regimens, but if they can’t afford the medications, what have we accomplished?”
SHM’s external benchmarks have provided an objective format for comparing and improving outcomes, Ms. Lautenbaugh said. “We like to see where we are and use the data to make significant improvements, but we’re also focused on internal assessments. If we make changes for a given metric, how does it affect performance in other areas?” One important metric is percentage of glucose readings within target range hospitalwide. “Our overall goal is 75%. It was 72% in April 2018, and we’ve raised it to 74.4%. It’s a small gain but it shows steady progress. Little steps make small but steady improvement,” she said.
“One area where we were not pleased was the occurrence of hypoglycemia,” Ms. Lautenbaugh said. “We did a root cause analysis of every hypoglycemic event, including several reports for patients who didn’t have diabetes at all. We had to weed out some that weren’t pertinent to our quality questions, but for those that are, the diabetes case manager calls the provider to make sure they were aware of the incident. We were able to identify the outliers in noncritical care, which we’re now able to tackle using a systematic approach.”
Get on the bus
Hospitalists are also integrally involved in a hospital glycemic improvement initiative at Orange Regional Medical Center (ORMC) in Middletown, N.Y.
The Glycemic Improvement Team (GIT) was formed in 2012 when a new hospital campus opened and EPIC was implemented as the hospital’s EMR. But glycemic control has taken on greater focus since 2015, when ORMC enrolled in eQUIPS, said Lorraine Porcaro, RN, the hospital’s diabetes clinical manager. The glycemic control team includes representatives from medicine, nursing, case management, laboratory, nutrition, pharmacy, wound care, and quality improvement.
Implementing the new EMR offered the opportunity to track a number of medical values in real time, Ms. Porcaro said. ORMC has focused its glycemic quality improvement efforts on hypoglycemia and hyperglycemia, with a recent emphasis on the need for improvements related to glucose reassessment 15 minutes post hypoglycemia treatment. More than a hundred “Diabetes Champions” have completed 16 hours of advanced training in diabetes and provide in-unit mentorship for other staff.
The ORMC team’s glycemic improvement “bus” is a rolling cart that goes from unit to unit supplying nurse education, reminders, copies of department-specific policies and protocols, and treats for staff. “It’s what we’re known for,” Ms. Porcaro said. Pens with the motto: “Don’t Miss the Bus! Retest in 15!” summarize the GIT’s current focus on post–hypoglycemia treatment retesting.
Hospitalists were part of the glycemic improvement process at ORMC from the beginning and are still involved, said Adrian Paraschiv, MD, FHM, a hospitalist and assistant director of the medical center, as well as the ORMC director of clinical information technology. ORMC initiated hospitalist coverage in 1998 and now has three HM groups, two of them represented on the glycemic improvement team.
“Like any hospital, we feel we should minimize hypoglycemic events,” Dr. Paraschiv explained. “This became important for other hospital departments, and we recognized we needed a major QI initiative to improve our outcomes hospitalwide. In the process, we noticed what other people were saying: Results from improving glycemic control included reduced length of stay, cost, and infections. That provided motivation for the hospital to support our initiative.”
Glucose management isn’t only about blood sugar, but whether the patient ate or not, their other blood work, the level of education for patient and staff, and a variety of other inputs, Dr. Paraschiv said. “All of these things were in the EMR but all over the place. EPIC had an incipient structure for pulling the data together, and we modified it to show everything that’s going on with the patient’s glycemic control on a single screen. We can build order sets and issue different reports.”
Today at ORMC, hypoglycemia is reassessed within 30 minutes more than 50% of the time. “It will never be at 100%, but we wanted to at least be at the national mean for eQUIPS hospitals. Our stretch goal was to be in the top quartile, and by the end of 2017, we realized that goal,” Ms. Porcaro said. Sometimes, because of changes in patients and staff, the GIT needs to repeat the education and review policies. “Since then, it’s been a matter of continuing staff education; sharing glucose data with stakeholders; talking about goals for ICU and non-ICU units; and, when needed, rolling out the bus.”
Participation in eQUIPS has made it possible to gather this information in one place and present it in a way that makes sense to physicians, Dr. Paraschiv said. “Dr. Maynard and SHM showed us how to put the data together to add value. Using these tools, we started looking at our processes, what needed to change, and what we are able to change. Now we’re examining what happens afterward. Can we use the electronic system to automatically alert physicians to make changes to the treatment regimen in real time? We continue to improve using upgrades to our EMR, such as an alert system with best practice advisories for the clinician. We now think we can actually achieve what we set out to achieve,” he said.
“Our idea was that we needed to market this program throughout the hospital – starting from the kitchen, meal delivery staff, IT, laboratory, medical and nursing staff,” Ms. Porcaro said. “The issue is multifactorial – it’s for the entire hospital. My heart is warmed when I see the woman who delivers the meals asking the patient: ‘Have you gotten your insulin shot?’ ”
References
1. Corvino L et al. “Management of diabetes and hyperglycemia in hospitalized patients.” Updated 2017 Oct 1 in De Groot LJ et al. editors. Endotext. South Dartmouth (MA): MDText.com 2000.
2. American Diabetes Association. Glycemic targets. Diabetes Care 2017 Jan;40(Suppl 1):S48-56.
3. Maynard G et al. “Design and implementation of a web-based reporting and benchmarking center for inpatient glucometrics.” J Diabetes Sci Technol. 2014 May 12;8(4):630-40.
Dolutegravir plus 3TC matches three drugs for HIV control
AMSTERDAM – A two-drug antiretroviral regimen with an integrase inhibitor was noninferior to a standard three-drug regimen for controlling HIV viral load in a pair of identical, phase 3, multicenter, randomized trials with more than 1,400 patients.
The efficacy and safety results seen in the two studies at the primary endpoint follow-up of 48 weeks support the tested combination of the integrase inhibitor dolutegravir (Tivicay) plus the nucleoside reverse transcriptase inhibitor (RTI) lamivudine (3TC, Epivir) as an “effective option,” Pedro Cahn, MD, said at the 22nd International AIDS Conference.
The two trials from which he reported results, GEMINI-1 and GEMINI-2, which both compared the dolutegravir (DTG) plus 3TC regimen against DTG plus the nucleotide RTI tenofovir (Viread) and the nucleoside RTI emtricitabine (Emtriva), together showed after 48 weeks on treatment a 91% rate of complete virologic response to DTG plus 3TC with fewer than 50 detectable HIV RNA copies per mL, compared with a 93% complete response among patients on DTG plus tenofovir and emtricitabine. The efficacy of the two-drug regimen fell within the prespecified definition of noninferiority, compared with the three-drug comparator arm, the primary endpoint for both studies, said Dr. Cahn, scientific director of Fundacion Huesped in Buenos Aires, and professor of infectious diseases at Buenos Aires University.
“This is the first time a randomized, controlled trial showed the noninferiority of a two-drug regimen, compared with a three-drug regimen while using an integrase inhibitor as the core drug,” Dr. Cahn said. The goal of cutting the treatment regimen down to two drugs is to “reduce drug burden” and potentially produce fewer adverse effects and reduce cost, he explained.
Integrase strand transport inhibitors like DTG make sense as the core drug because “as a class they quickly reduce viral load” and have several other very attractive properties including good tolerability, a high barrier to resistance mutations, quick recovery of CD4 cell levels, and good adherence by patients, said Dr. Cahn. These advantages apply not only to DTG but also to other drugs in the class: raltegravir (Isentress), elvitegravir (Vitekta), and bictegravir (Biktarvy). Integrase inhibitors have been specified as part of the preferred anti-HIV regimen for most people starting HIV treatment by public health officials in several countries as well as by the World Health Organization in its 2018 revised HIV treatment recommendations.
But Dr. Cahn put a few qualifications on the findings so far for the combination of DTG and 3TC. Its durability has been tested out only to 48 weeks, although during that time no resistant HIV was seen. The studies will continue to follow the patients on dual treatment for as long as 144 weeks, he said. Also, the two-drug regimen should be considered, for the time being, only for patients who match the enrollment criteria for the GEMINI trials: Patients with a viral load no greater than 500,000 RNA copies/mL, no prior treatment, no evidence of preexisting viral resistance to any anti-HIV drugs, and no hepatitis B virus infection or need for hepatitis C virus treatment. Also there is uncertainty about the risk that women who become pregnant while on DTG have for giving birth to an infant with a neural tube defect. A recent report documented preliminary evidence for an increased risk (N Engl J Med. 2018 Jul 24. doi: 10.1056/NEJMc180765).
In addition to its noninferior efficacy, compared with a triple-drug regimen, the dual regimen showed good safety and tolerance, with a 7% incidence of serious adverse events and a 2% rate of events leading to withdrawal of treatment, rates similar to the triple-drug arm. The dual regimen also showed less evidence for renal damage than the triple regimen, including a statistically significant smaller drop in glomerular filtration rate than the triple regimen and no spikes in urine markers of renal damage as occurred on three drugs. Two drugs also induced no increases in markers of bone metabolism, but this happened with three drugs, Dr. Cahn reported.
The combined data from the two GEMINI studies enrolled 1,433 HIV-infected patients at centers in 21 countries including several U.S. centers. Patients averaged about 33 years old, 85% were men, and more than 90% had a CD4 cell count greater than 200 cell/mL at enrollment. Eighty percent had a viral load of no more than 100,00 RNA copies/mL, and the 20% with higher viral loads were stratified in equal numbers into the two treatment arms.
The 91% and 93% virologic response rates in the two treatment arms came in the intention-to-treat analysis and correlated with similar average rises among patients in the two arms in CD4 cell counts after 48 weeks of 224-228 cell/mm3. In the per protocol analysis the virologic response rates were 93% with the dual regimen and 94% with the triple regimen
SOURCE: Cahn P et al. AIDS 2018, Abstract 13210.
AMSTERDAM – A two-drug antiretroviral regimen with an integrase inhibitor was noninferior to a standard three-drug regimen for controlling HIV viral load in a pair of identical, phase 3, multicenter, randomized trials with more than 1,400 patients.
The efficacy and safety results seen in the two studies at the primary endpoint follow-up of 48 weeks support the tested combination of the integrase inhibitor dolutegravir (Tivicay) plus the nucleoside reverse transcriptase inhibitor (RTI) lamivudine (3TC, Epivir) as an “effective option,” Pedro Cahn, MD, said at the 22nd International AIDS Conference.
The two trials from which he reported results, GEMINI-1 and GEMINI-2, which both compared the dolutegravir (DTG) plus 3TC regimen against DTG plus the nucleotide RTI tenofovir (Viread) and the nucleoside RTI emtricitabine (Emtriva), together showed after 48 weeks on treatment a 91% rate of complete virologic response to DTG plus 3TC with fewer than 50 detectable HIV RNA copies per mL, compared with a 93% complete response among patients on DTG plus tenofovir and emtricitabine. The efficacy of the two-drug regimen fell within the prespecified definition of noninferiority, compared with the three-drug comparator arm, the primary endpoint for both studies, said Dr. Cahn, scientific director of Fundacion Huesped in Buenos Aires, and professor of infectious diseases at Buenos Aires University.
“This is the first time a randomized, controlled trial showed the noninferiority of a two-drug regimen, compared with a three-drug regimen while using an integrase inhibitor as the core drug,” Dr. Cahn said. The goal of cutting the treatment regimen down to two drugs is to “reduce drug burden” and potentially produce fewer adverse effects and reduce cost, he explained.
Integrase strand transport inhibitors like DTG make sense as the core drug because “as a class they quickly reduce viral load” and have several other very attractive properties including good tolerability, a high barrier to resistance mutations, quick recovery of CD4 cell levels, and good adherence by patients, said Dr. Cahn. These advantages apply not only to DTG but also to other drugs in the class: raltegravir (Isentress), elvitegravir (Vitekta), and bictegravir (Biktarvy). Integrase inhibitors have been specified as part of the preferred anti-HIV regimen for most people starting HIV treatment by public health officials in several countries as well as by the World Health Organization in its 2018 revised HIV treatment recommendations.
But Dr. Cahn put a few qualifications on the findings so far for the combination of DTG and 3TC. Its durability has been tested out only to 48 weeks, although during that time no resistant HIV was seen. The studies will continue to follow the patients on dual treatment for as long as 144 weeks, he said. Also, the two-drug regimen should be considered, for the time being, only for patients who match the enrollment criteria for the GEMINI trials: Patients with a viral load no greater than 500,000 RNA copies/mL, no prior treatment, no evidence of preexisting viral resistance to any anti-HIV drugs, and no hepatitis B virus infection or need for hepatitis C virus treatment. Also there is uncertainty about the risk that women who become pregnant while on DTG have for giving birth to an infant with a neural tube defect. A recent report documented preliminary evidence for an increased risk (N Engl J Med. 2018 Jul 24. doi: 10.1056/NEJMc180765).
In addition to its noninferior efficacy, compared with a triple-drug regimen, the dual regimen showed good safety and tolerance, with a 7% incidence of serious adverse events and a 2% rate of events leading to withdrawal of treatment, rates similar to the triple-drug arm. The dual regimen also showed less evidence for renal damage than the triple regimen, including a statistically significant smaller drop in glomerular filtration rate than the triple regimen and no spikes in urine markers of renal damage as occurred on three drugs. Two drugs also induced no increases in markers of bone metabolism, but this happened with three drugs, Dr. Cahn reported.
The combined data from the two GEMINI studies enrolled 1,433 HIV-infected patients at centers in 21 countries including several U.S. centers. Patients averaged about 33 years old, 85% were men, and more than 90% had a CD4 cell count greater than 200 cell/mL at enrollment. Eighty percent had a viral load of no more than 100,00 RNA copies/mL, and the 20% with higher viral loads were stratified in equal numbers into the two treatment arms.
The 91% and 93% virologic response rates in the two treatment arms came in the intention-to-treat analysis and correlated with similar average rises among patients in the two arms in CD4 cell counts after 48 weeks of 224-228 cell/mm3. In the per protocol analysis the virologic response rates were 93% with the dual regimen and 94% with the triple regimen
SOURCE: Cahn P et al. AIDS 2018, Abstract 13210.
AMSTERDAM – A two-drug antiretroviral regimen with an integrase inhibitor was noninferior to a standard three-drug regimen for controlling HIV viral load in a pair of identical, phase 3, multicenter, randomized trials with more than 1,400 patients.
The efficacy and safety results seen in the two studies at the primary endpoint follow-up of 48 weeks support the tested combination of the integrase inhibitor dolutegravir (Tivicay) plus the nucleoside reverse transcriptase inhibitor (RTI) lamivudine (3TC, Epivir) as an “effective option,” Pedro Cahn, MD, said at the 22nd International AIDS Conference.
The two trials from which he reported results, GEMINI-1 and GEMINI-2, which both compared the dolutegravir (DTG) plus 3TC regimen against DTG plus the nucleotide RTI tenofovir (Viread) and the nucleoside RTI emtricitabine (Emtriva), together showed after 48 weeks on treatment a 91% rate of complete virologic response to DTG plus 3TC with fewer than 50 detectable HIV RNA copies per mL, compared with a 93% complete response among patients on DTG plus tenofovir and emtricitabine. The efficacy of the two-drug regimen fell within the prespecified definition of noninferiority, compared with the three-drug comparator arm, the primary endpoint for both studies, said Dr. Cahn, scientific director of Fundacion Huesped in Buenos Aires, and professor of infectious diseases at Buenos Aires University.
“This is the first time a randomized, controlled trial showed the noninferiority of a two-drug regimen, compared with a three-drug regimen while using an integrase inhibitor as the core drug,” Dr. Cahn said. The goal of cutting the treatment regimen down to two drugs is to “reduce drug burden” and potentially produce fewer adverse effects and reduce cost, he explained.
Integrase strand transport inhibitors like DTG make sense as the core drug because “as a class they quickly reduce viral load” and have several other very attractive properties including good tolerability, a high barrier to resistance mutations, quick recovery of CD4 cell levels, and good adherence by patients, said Dr. Cahn. These advantages apply not only to DTG but also to other drugs in the class: raltegravir (Isentress), elvitegravir (Vitekta), and bictegravir (Biktarvy). Integrase inhibitors have been specified as part of the preferred anti-HIV regimen for most people starting HIV treatment by public health officials in several countries as well as by the World Health Organization in its 2018 revised HIV treatment recommendations.
But Dr. Cahn put a few qualifications on the findings so far for the combination of DTG and 3TC. Its durability has been tested out only to 48 weeks, although during that time no resistant HIV was seen. The studies will continue to follow the patients on dual treatment for as long as 144 weeks, he said. Also, the two-drug regimen should be considered, for the time being, only for patients who match the enrollment criteria for the GEMINI trials: Patients with a viral load no greater than 500,000 RNA copies/mL, no prior treatment, no evidence of preexisting viral resistance to any anti-HIV drugs, and no hepatitis B virus infection or need for hepatitis C virus treatment. Also there is uncertainty about the risk that women who become pregnant while on DTG have for giving birth to an infant with a neural tube defect. A recent report documented preliminary evidence for an increased risk (N Engl J Med. 2018 Jul 24. doi: 10.1056/NEJMc180765).
In addition to its noninferior efficacy, compared with a triple-drug regimen, the dual regimen showed good safety and tolerance, with a 7% incidence of serious adverse events and a 2% rate of events leading to withdrawal of treatment, rates similar to the triple-drug arm. The dual regimen also showed less evidence for renal damage than the triple regimen, including a statistically significant smaller drop in glomerular filtration rate than the triple regimen and no spikes in urine markers of renal damage as occurred on three drugs. Two drugs also induced no increases in markers of bone metabolism, but this happened with three drugs, Dr. Cahn reported.
The combined data from the two GEMINI studies enrolled 1,433 HIV-infected patients at centers in 21 countries including several U.S. centers. Patients averaged about 33 years old, 85% were men, and more than 90% had a CD4 cell count greater than 200 cell/mL at enrollment. Eighty percent had a viral load of no more than 100,00 RNA copies/mL, and the 20% with higher viral loads were stratified in equal numbers into the two treatment arms.
The 91% and 93% virologic response rates in the two treatment arms came in the intention-to-treat analysis and correlated with similar average rises among patients in the two arms in CD4 cell counts after 48 weeks of 224-228 cell/mm3. In the per protocol analysis the virologic response rates were 93% with the dual regimen and 94% with the triple regimen
SOURCE: Cahn P et al. AIDS 2018, Abstract 13210.
REPORTING FROM AIDS 2018
Key clinical point: The reduction in HIV by dolutegravir plus lamivudine was noninferior to the reduction by dolutegravir plus tenofovir and emtricitabine.
Major finding: HIV levels became undetectable in 91% of patients on dolutegravir plus lamivudine and in 93% on dolutegravir, tenofivir, and emtricitabine.
Study details: GEMINI-1 and GEMINI-2, two identical randomized, multicenter, randomized phase 3 trials with a total of 1,433 HIV-infected patients.
Disclosures: The GEMINI-1 and -2 trials were sponsored by GlaxoSmithKline and Viiv Healthcare, the company that markets dolutegravir (Tivicay). Dr. Cahn has been an advisor to or speaker for Abbvie, Merck, and Viiv, and he has received research funding from Abbvie, Merck, Richmond, and Viiv.
Source: Cahn P et al. AIDS 2018, Abstract 13210.
Shared decision making falls short for lung cancer screening
A small study of discussions between clinicians and patients about has highlighted a lack of shared decision making and information about potential harms.
“Our findings are consistent with increasingly robust evidence that patients, members of the public, and clinicians tend to overestimate the benefits and underestimate the harms of medical interventions, including treatments, tests, or screening tests,” wrote Alison T. Brenner, PhD, and her colleagues at the University of North Carolina at Chapel Hill, in a presentation of the findings in JAMA Internal Medicine.
The researchers transcribed conversations between 14 patients – who were eligible for lung cancer screening because of their age – and their primary care or pulmonary care physicians. They found that not one physician adequately explained false positives or their consequences, such as the possibility of additional imaging and invasive diagnostic procedures, nor did any discuss the potential for diagnosis and treatment of cancer that would not have affected the individual during his or her lifetime (overdiagnosis).
Researchers used a 12-item scoring system for physician behaviors, with 0-4 points allocated to each item. The items included telling patients there was more than one way to deal with the identified problem, explaining the pros and cons of the available options, exploring patients’ fears and concerns, and offering the patient clear opportunities to ask questions.
Mean scores for each item ranged from 0 to 0.79. Two conversations met the baseline skill criteria – a score of two points – for one item each, two other conversations met the baseline skill criteria for two items. But for 8 of the 12 items, not one conversation achieved even a baseline skill score. The mean total visit length was 13:07 minutes, and the mean time spent discussing LCS was 0:59 minute (range, 0:16-2:19 minutes).
“Although experts disagree on how well the existing evidence suggests an overall net benefit of LCS [lung cancer screening], consensus has emerged on the importance of shared decision making,” wrote the investigators. Current U.S. Preventive Services Task Force recommendations stress that lung cancer screening should not occur without a shared decision-making process, including a thorough discussion of benefits and harms.
The authors said that, while their study was small, it did raise concerns that shared decision making in practice is a long way from what is recommended by the guidelines.
“The fact that the main drivers of harms from LCS (false positives and their sequelae, as well as overdiagnosis) were not adequately explained by physicians is troubling,” they wrote. “However, these findings are consistent with other evidence that discussions between patients and physicians regarding preference-sensitive cancer screening decisions are imbalanced with respect to explaining the pros and cons.”
Based on these findings, the authors called for urgent discussions between clinical leaders, policy makers, and researchers about how to involve patients more meaningfully in discussions about lung cancer screening.
“Until more is known, we believe that guideline and policy makers should not assume that recommending SDM [shared decision-making] for cancer-screening decisions with a ‘tenuous balance of benefits and harms,’ like LCS, will protect patients who would value avoiding screening harms.”
The study was supported by the North Carolina Translational and Clinical Sciences Institute and the National Cancer Institute. No conflicts of interest were declared.
SOURCE: Brenner A et al. JAMA Intern Med. 2018; Aug 13. doi: 10.1001/jamainternmed.2018.3054.
The results of this first real-world study of the U.S. Preventive Services Task Force recommendations on lung cancer screening – which comes 4 years after the recommendations were made – are disappointing. Even the highest-scoring conversations made no mention of possible harms, such as a 98% false-positive rate, additional testing, and the small increased cancer risk from radiation.
Rita F. Redberg, MD, is from the department of medicine in the division of cardiology at the University of California, San Francisco, and the editor of JAMA Internal Medicine. These comments are taken from an accompanying editorial (JAMA Int Med. 2018 Aug 13. doi: 10.1001/jamainternmed.2018.3527). Dr. Redberg chaired the April 2014 Medicare Evidence Development & Coverage Advisory Committee meeting on lung cancer screening.
The results of this first real-world study of the U.S. Preventive Services Task Force recommendations on lung cancer screening – which comes 4 years after the recommendations were made – are disappointing. Even the highest-scoring conversations made no mention of possible harms, such as a 98% false-positive rate, additional testing, and the small increased cancer risk from radiation.
Rita F. Redberg, MD, is from the department of medicine in the division of cardiology at the University of California, San Francisco, and the editor of JAMA Internal Medicine. These comments are taken from an accompanying editorial (JAMA Int Med. 2018 Aug 13. doi: 10.1001/jamainternmed.2018.3527). Dr. Redberg chaired the April 2014 Medicare Evidence Development & Coverage Advisory Committee meeting on lung cancer screening.
The results of this first real-world study of the U.S. Preventive Services Task Force recommendations on lung cancer screening – which comes 4 years after the recommendations were made – are disappointing. Even the highest-scoring conversations made no mention of possible harms, such as a 98% false-positive rate, additional testing, and the small increased cancer risk from radiation.
Rita F. Redberg, MD, is from the department of medicine in the division of cardiology at the University of California, San Francisco, and the editor of JAMA Internal Medicine. These comments are taken from an accompanying editorial (JAMA Int Med. 2018 Aug 13. doi: 10.1001/jamainternmed.2018.3527). Dr. Redberg chaired the April 2014 Medicare Evidence Development & Coverage Advisory Committee meeting on lung cancer screening.
A small study of discussions between clinicians and patients about has highlighted a lack of shared decision making and information about potential harms.
“Our findings are consistent with increasingly robust evidence that patients, members of the public, and clinicians tend to overestimate the benefits and underestimate the harms of medical interventions, including treatments, tests, or screening tests,” wrote Alison T. Brenner, PhD, and her colleagues at the University of North Carolina at Chapel Hill, in a presentation of the findings in JAMA Internal Medicine.
The researchers transcribed conversations between 14 patients – who were eligible for lung cancer screening because of their age – and their primary care or pulmonary care physicians. They found that not one physician adequately explained false positives or their consequences, such as the possibility of additional imaging and invasive diagnostic procedures, nor did any discuss the potential for diagnosis and treatment of cancer that would not have affected the individual during his or her lifetime (overdiagnosis).
Researchers used a 12-item scoring system for physician behaviors, with 0-4 points allocated to each item. The items included telling patients there was more than one way to deal with the identified problem, explaining the pros and cons of the available options, exploring patients’ fears and concerns, and offering the patient clear opportunities to ask questions.
Mean scores for each item ranged from 0 to 0.79. Two conversations met the baseline skill criteria – a score of two points – for one item each, two other conversations met the baseline skill criteria for two items. But for 8 of the 12 items, not one conversation achieved even a baseline skill score. The mean total visit length was 13:07 minutes, and the mean time spent discussing LCS was 0:59 minute (range, 0:16-2:19 minutes).
“Although experts disagree on how well the existing evidence suggests an overall net benefit of LCS [lung cancer screening], consensus has emerged on the importance of shared decision making,” wrote the investigators. Current U.S. Preventive Services Task Force recommendations stress that lung cancer screening should not occur without a shared decision-making process, including a thorough discussion of benefits and harms.
The authors said that, while their study was small, it did raise concerns that shared decision making in practice is a long way from what is recommended by the guidelines.
“The fact that the main drivers of harms from LCS (false positives and their sequelae, as well as overdiagnosis) were not adequately explained by physicians is troubling,” they wrote. “However, these findings are consistent with other evidence that discussions between patients and physicians regarding preference-sensitive cancer screening decisions are imbalanced with respect to explaining the pros and cons.”
Based on these findings, the authors called for urgent discussions between clinical leaders, policy makers, and researchers about how to involve patients more meaningfully in discussions about lung cancer screening.
“Until more is known, we believe that guideline and policy makers should not assume that recommending SDM [shared decision-making] for cancer-screening decisions with a ‘tenuous balance of benefits and harms,’ like LCS, will protect patients who would value avoiding screening harms.”
The study was supported by the North Carolina Translational and Clinical Sciences Institute and the National Cancer Institute. No conflicts of interest were declared.
SOURCE: Brenner A et al. JAMA Intern Med. 2018; Aug 13. doi: 10.1001/jamainternmed.2018.3054.
A small study of discussions between clinicians and patients about has highlighted a lack of shared decision making and information about potential harms.
“Our findings are consistent with increasingly robust evidence that patients, members of the public, and clinicians tend to overestimate the benefits and underestimate the harms of medical interventions, including treatments, tests, or screening tests,” wrote Alison T. Brenner, PhD, and her colleagues at the University of North Carolina at Chapel Hill, in a presentation of the findings in JAMA Internal Medicine.
The researchers transcribed conversations between 14 patients – who were eligible for lung cancer screening because of their age – and their primary care or pulmonary care physicians. They found that not one physician adequately explained false positives or their consequences, such as the possibility of additional imaging and invasive diagnostic procedures, nor did any discuss the potential for diagnosis and treatment of cancer that would not have affected the individual during his or her lifetime (overdiagnosis).
Researchers used a 12-item scoring system for physician behaviors, with 0-4 points allocated to each item. The items included telling patients there was more than one way to deal with the identified problem, explaining the pros and cons of the available options, exploring patients’ fears and concerns, and offering the patient clear opportunities to ask questions.
Mean scores for each item ranged from 0 to 0.79. Two conversations met the baseline skill criteria – a score of two points – for one item each, two other conversations met the baseline skill criteria for two items. But for 8 of the 12 items, not one conversation achieved even a baseline skill score. The mean total visit length was 13:07 minutes, and the mean time spent discussing LCS was 0:59 minute (range, 0:16-2:19 minutes).
“Although experts disagree on how well the existing evidence suggests an overall net benefit of LCS [lung cancer screening], consensus has emerged on the importance of shared decision making,” wrote the investigators. Current U.S. Preventive Services Task Force recommendations stress that lung cancer screening should not occur without a shared decision-making process, including a thorough discussion of benefits and harms.
The authors said that, while their study was small, it did raise concerns that shared decision making in practice is a long way from what is recommended by the guidelines.
“The fact that the main drivers of harms from LCS (false positives and their sequelae, as well as overdiagnosis) were not adequately explained by physicians is troubling,” they wrote. “However, these findings are consistent with other evidence that discussions between patients and physicians regarding preference-sensitive cancer screening decisions are imbalanced with respect to explaining the pros and cons.”
Based on these findings, the authors called for urgent discussions between clinical leaders, policy makers, and researchers about how to involve patients more meaningfully in discussions about lung cancer screening.
“Until more is known, we believe that guideline and policy makers should not assume that recommending SDM [shared decision-making] for cancer-screening decisions with a ‘tenuous balance of benefits and harms,’ like LCS, will protect patients who would value avoiding screening harms.”
The study was supported by the North Carolina Translational and Clinical Sciences Institute and the National Cancer Institute. No conflicts of interest were declared.
SOURCE: Brenner A et al. JAMA Intern Med. 2018; Aug 13. doi: 10.1001/jamainternmed.2018.3054.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Few clinicians are following recommendations about shared decision-making with patients regarding lung cancer screening.
Major finding: No physicians in the study explained false positives and their risks in discussions with patients about lung cancer screening.
Study details: Content analysis of 14 recorded consultations about lung cancer screening.
Disclosures: The study was supported by the North Carolina Translational and Clinical Sciences Institute and the National Cancer Institute. No conflicts of interest were declared.
Source: Brenner A et al. JAMA Intern Med. 2018; Aug 13. doi: 10.1001/jamainternmed.2018.3054.
No increase in autism risk with prenatal Tdap
A retrospective cohort study in more than 80,000 children has found no evidence of an increased risk of autism spectrum disorder associated with prenatal tetanus, diphtheria, and acellular pertussis (Tdap) immunization.
Of 81,993 children born between 2011 and 2014, 1,341 children (1.6%) were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 3.78 per 1,000 person-years in the Tdap-vaccinated group, and 4.05 per 1,000 person years in the unvaccinated group, representing an unadjusted hazard ratio of 0.98 and an adjusted hazard ratio of 0.85. This was consistent across all the birth cohorts.
Prenatal immunization rates with the prenatal Tdap vaccine ranged from 26% of the 2012 birth cohort to 79% of the 2014 birth cohort, and mean gestational age at vaccination was 28 weeks.
Tracy A. Becerra-Culqui, PhD, MPH, and colleagues of the department of research and evaluation at Kaiser Permanente Southern California, Pasadena, said this was the first study to look at the risk of autism spectrum disorder after maternal exposure to the Tdap vaccine, to their knowledge. “Our results potentially indicate that the maternal Tdap vaccine affects immune trajectories protecting infants against infections that would otherwise lead to neurodevelopmental alterations.”
They highlighted several strengths of their study. One was that maternal Tdap vaccination and information on autism spectrum disorder both were derived from EHRs and therefore not subject to recall bias. The study, published online in Pediatrics, also included children diagnosed with autism spectrum disorder from age 1 year onwards, reflecting the latest evidence on screening and diagnosis of autism.
“Our weighting procedures enabled us to balance the Tdap-exposed and -unexposed groups to compare two populations that were comparable in important measured confounding factors,” Dr. Becerra-Culqui and associates noted.
The investigators found that women who received the Tdap vaccine during pregnancy were more likely to be Asian American or Pacific Islander, to have a bachelor’s degree or higher, be nulliparous, to have also been vaccinated prenatally against influenza, and to deliver at term, compared with unvaccinated women.
However the authors did note that their follow-up was limited to 6.5 years for the earliest birth cohort, and 3.5 years for the latest cohort, so they may not have picked up children who received a later diagnosis of autism spectrum disorder.
The study was supported by Kaiser Permanente Southern California. Five authors declared funding from GlaxoSmithKline, Bayer AG, or the Centers for Disease Control and Prevention for unrelated or separate studies.
SOURCE: Becerra-Culqui T et al. Pediatrics. 2018;142(3):e20180120.
A retrospective cohort study in more than 80,000 children has found no evidence of an increased risk of autism spectrum disorder associated with prenatal tetanus, diphtheria, and acellular pertussis (Tdap) immunization.
Of 81,993 children born between 2011 and 2014, 1,341 children (1.6%) were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 3.78 per 1,000 person-years in the Tdap-vaccinated group, and 4.05 per 1,000 person years in the unvaccinated group, representing an unadjusted hazard ratio of 0.98 and an adjusted hazard ratio of 0.85. This was consistent across all the birth cohorts.
Prenatal immunization rates with the prenatal Tdap vaccine ranged from 26% of the 2012 birth cohort to 79% of the 2014 birth cohort, and mean gestational age at vaccination was 28 weeks.
Tracy A. Becerra-Culqui, PhD, MPH, and colleagues of the department of research and evaluation at Kaiser Permanente Southern California, Pasadena, said this was the first study to look at the risk of autism spectrum disorder after maternal exposure to the Tdap vaccine, to their knowledge. “Our results potentially indicate that the maternal Tdap vaccine affects immune trajectories protecting infants against infections that would otherwise lead to neurodevelopmental alterations.”
They highlighted several strengths of their study. One was that maternal Tdap vaccination and information on autism spectrum disorder both were derived from EHRs and therefore not subject to recall bias. The study, published online in Pediatrics, also included children diagnosed with autism spectrum disorder from age 1 year onwards, reflecting the latest evidence on screening and diagnosis of autism.
“Our weighting procedures enabled us to balance the Tdap-exposed and -unexposed groups to compare two populations that were comparable in important measured confounding factors,” Dr. Becerra-Culqui and associates noted.
The investigators found that women who received the Tdap vaccine during pregnancy were more likely to be Asian American or Pacific Islander, to have a bachelor’s degree or higher, be nulliparous, to have also been vaccinated prenatally against influenza, and to deliver at term, compared with unvaccinated women.
However the authors did note that their follow-up was limited to 6.5 years for the earliest birth cohort, and 3.5 years for the latest cohort, so they may not have picked up children who received a later diagnosis of autism spectrum disorder.
The study was supported by Kaiser Permanente Southern California. Five authors declared funding from GlaxoSmithKline, Bayer AG, or the Centers for Disease Control and Prevention for unrelated or separate studies.
SOURCE: Becerra-Culqui T et al. Pediatrics. 2018;142(3):e20180120.
A retrospective cohort study in more than 80,000 children has found no evidence of an increased risk of autism spectrum disorder associated with prenatal tetanus, diphtheria, and acellular pertussis (Tdap) immunization.
Of 81,993 children born between 2011 and 2014, 1,341 children (1.6%) were diagnosed with autism spectrum disorder. The incidence of autism spectrum disorder was 3.78 per 1,000 person-years in the Tdap-vaccinated group, and 4.05 per 1,000 person years in the unvaccinated group, representing an unadjusted hazard ratio of 0.98 and an adjusted hazard ratio of 0.85. This was consistent across all the birth cohorts.
Prenatal immunization rates with the prenatal Tdap vaccine ranged from 26% of the 2012 birth cohort to 79% of the 2014 birth cohort, and mean gestational age at vaccination was 28 weeks.
Tracy A. Becerra-Culqui, PhD, MPH, and colleagues of the department of research and evaluation at Kaiser Permanente Southern California, Pasadena, said this was the first study to look at the risk of autism spectrum disorder after maternal exposure to the Tdap vaccine, to their knowledge. “Our results potentially indicate that the maternal Tdap vaccine affects immune trajectories protecting infants against infections that would otherwise lead to neurodevelopmental alterations.”
They highlighted several strengths of their study. One was that maternal Tdap vaccination and information on autism spectrum disorder both were derived from EHRs and therefore not subject to recall bias. The study, published online in Pediatrics, also included children diagnosed with autism spectrum disorder from age 1 year onwards, reflecting the latest evidence on screening and diagnosis of autism.
“Our weighting procedures enabled us to balance the Tdap-exposed and -unexposed groups to compare two populations that were comparable in important measured confounding factors,” Dr. Becerra-Culqui and associates noted.
The investigators found that women who received the Tdap vaccine during pregnancy were more likely to be Asian American or Pacific Islander, to have a bachelor’s degree or higher, be nulliparous, to have also been vaccinated prenatally against influenza, and to deliver at term, compared with unvaccinated women.
However the authors did note that their follow-up was limited to 6.5 years for the earliest birth cohort, and 3.5 years for the latest cohort, so they may not have picked up children who received a later diagnosis of autism spectrum disorder.
The study was supported by Kaiser Permanente Southern California. Five authors declared funding from GlaxoSmithKline, Bayer AG, or the Centers for Disease Control and Prevention for unrelated or separate studies.
SOURCE: Becerra-Culqui T et al. Pediatrics. 2018;142(3):e20180120.
FROM PEDIATRICS
Key clinical point:
Major finding: The adjusted hazard ratio for autism spectrum disorder in children exposed to the prenatal Tdap vaccine is 0.98, compared with unvaccinated children.
Study details: A retrospective cohort study in 81,993 children exposed to the prenatal Tdap vaccine.
Disclosures: The study was supported by Kaiser Permanente Southern California. Five authors declared funding from GlaxoSmithKline, Bayer AG, or the Centers for Disease Control and Prevention for unrelated or separate studies.
Source: Becerra-Culqui T et al. Pediatrics. 2018;142(3):e20180120.
Varied diet not necessarily a high-quality one
A diverse diet is not necessarily a healthy one, according to an advisory issued by the American Heart Association that has instead emphasized the importance of a healthy eating pattern.
Published in the Aug. 9 online edition of Circulation, the science advisory was prompted by emerging evidence that greater dietary diversity may actually be associated with eating more poor quality foods and higher energy intake, especially among middle-aged adults.
Researchers conducted a literature search across 2000-2017 for studies of dietary diversity – defined as the number of different foods or food groups eaten over a given period of time – and dietary quality.
However, they also noted that many studies had significant limitations that contributed to high levels of inconsistency across all studies.
For example, one study in overweight and obese individuals found increasing dietary diversity was associated with a decrease in body mass index but with respect to intakes of only low–energy dense foods. Another study in Chinese adults saw an increase in diversity in the intake of snacks but not grains, vegetables, fruits, meats, or beverages, and this was associated with a 45% greater odds of being overweight, compared with individuals with a lower diversity of snack consumption.
Similarly, an observational study in 2,505 U.S. adults found individuals in the highest quintile of dietary diversity had a 120% greater gain in waist circumference, compared with those in the lowest quintile.
“Associations with dissimilarity scores are consistent with evidence from feeding studies showing that exposure to foods with different characteristics led to increased energy intake, which may partially explain gain in waist circumference over time,” wrote Marcia C. de Oliveira Otto, PhD, from the University of Texas Health Science Centre at Houston and coauthors.
The same was seen in short-term interventional studies, where most showed that having access to a wider variety of foods actually led to an increase in intake, compared with being served only a single food.
For example, one study showed adults offered a second course of sandwiches with different fillings to the first course actually ate 30% more than those served the same option for both courses.
Another study randomized overweight and obese adults to an unlimited number of snack options consumed less than once a day, or any amount of one favored snack option, with all snacks being within a daily caloric goal. This study found that, over the course of 8 weeks, participants offered a variety of snacks ate 25% more servings than those with the one snack type.
The authors suggested that variety amplifies sensory stimulation and decreases satiety.
“Although calorie restriction goals were achieved in both groups, a significant increase in sensory-specific satiety and monotony ratings over time was observed in participants assigned to the one-snack option but not in participants assigned to a variety of snacks,” they wrote.
The relationship between dietary diversity and dietary quality is also complex. Investigators for a cross-sectional study in China found less-than-optimal consumption of the nine food groups in the Chinese dietary guidelines – in particular, fruits, vegetables, fish, and dairy – in diets with higher diversity scores.
“Overall, limited evidence shows no benefit to diet quality or diet healthfulness associated with increased food count or with a more even distribution of energy across foods, whereas findings from one observational study suggest that greater dissimilarity in foods consumed may be inversely associated with a healthy eating pattern.”
In conclusion, the advisory committee said that it was more appropriate to promote a healthy eating pattern, emphasizing intake of plant foods, protein sources, low-fat dairy, vegetable oils, and nuts.
One author declared research funding from the Hass Avocado Board. No other relevant conflicts of interest were declared.
SOURCE: de Oliveira Otto MC et al. Circulation. 2018 Aug. 9. doi: 10.1161/CIR.0000000000000595.
A diverse diet is not necessarily a healthy one, according to an advisory issued by the American Heart Association that has instead emphasized the importance of a healthy eating pattern.
Published in the Aug. 9 online edition of Circulation, the science advisory was prompted by emerging evidence that greater dietary diversity may actually be associated with eating more poor quality foods and higher energy intake, especially among middle-aged adults.
Researchers conducted a literature search across 2000-2017 for studies of dietary diversity – defined as the number of different foods or food groups eaten over a given period of time – and dietary quality.
However, they also noted that many studies had significant limitations that contributed to high levels of inconsistency across all studies.
For example, one study in overweight and obese individuals found increasing dietary diversity was associated with a decrease in body mass index but with respect to intakes of only low–energy dense foods. Another study in Chinese adults saw an increase in diversity in the intake of snacks but not grains, vegetables, fruits, meats, or beverages, and this was associated with a 45% greater odds of being overweight, compared with individuals with a lower diversity of snack consumption.
Similarly, an observational study in 2,505 U.S. adults found individuals in the highest quintile of dietary diversity had a 120% greater gain in waist circumference, compared with those in the lowest quintile.
“Associations with dissimilarity scores are consistent with evidence from feeding studies showing that exposure to foods with different characteristics led to increased energy intake, which may partially explain gain in waist circumference over time,” wrote Marcia C. de Oliveira Otto, PhD, from the University of Texas Health Science Centre at Houston and coauthors.
The same was seen in short-term interventional studies, where most showed that having access to a wider variety of foods actually led to an increase in intake, compared with being served only a single food.
For example, one study showed adults offered a second course of sandwiches with different fillings to the first course actually ate 30% more than those served the same option for both courses.
Another study randomized overweight and obese adults to an unlimited number of snack options consumed less than once a day, or any amount of one favored snack option, with all snacks being within a daily caloric goal. This study found that, over the course of 8 weeks, participants offered a variety of snacks ate 25% more servings than those with the one snack type.
The authors suggested that variety amplifies sensory stimulation and decreases satiety.
“Although calorie restriction goals were achieved in both groups, a significant increase in sensory-specific satiety and monotony ratings over time was observed in participants assigned to the one-snack option but not in participants assigned to a variety of snacks,” they wrote.
The relationship between dietary diversity and dietary quality is also complex. Investigators for a cross-sectional study in China found less-than-optimal consumption of the nine food groups in the Chinese dietary guidelines – in particular, fruits, vegetables, fish, and dairy – in diets with higher diversity scores.
“Overall, limited evidence shows no benefit to diet quality or diet healthfulness associated with increased food count or with a more even distribution of energy across foods, whereas findings from one observational study suggest that greater dissimilarity in foods consumed may be inversely associated with a healthy eating pattern.”
In conclusion, the advisory committee said that it was more appropriate to promote a healthy eating pattern, emphasizing intake of plant foods, protein sources, low-fat dairy, vegetable oils, and nuts.
One author declared research funding from the Hass Avocado Board. No other relevant conflicts of interest were declared.
SOURCE: de Oliveira Otto MC et al. Circulation. 2018 Aug. 9. doi: 10.1161/CIR.0000000000000595.
A diverse diet is not necessarily a healthy one, according to an advisory issued by the American Heart Association that has instead emphasized the importance of a healthy eating pattern.
Published in the Aug. 9 online edition of Circulation, the science advisory was prompted by emerging evidence that greater dietary diversity may actually be associated with eating more poor quality foods and higher energy intake, especially among middle-aged adults.
Researchers conducted a literature search across 2000-2017 for studies of dietary diversity – defined as the number of different foods or food groups eaten over a given period of time – and dietary quality.
However, they also noted that many studies had significant limitations that contributed to high levels of inconsistency across all studies.
For example, one study in overweight and obese individuals found increasing dietary diversity was associated with a decrease in body mass index but with respect to intakes of only low–energy dense foods. Another study in Chinese adults saw an increase in diversity in the intake of snacks but not grains, vegetables, fruits, meats, or beverages, and this was associated with a 45% greater odds of being overweight, compared with individuals with a lower diversity of snack consumption.
Similarly, an observational study in 2,505 U.S. adults found individuals in the highest quintile of dietary diversity had a 120% greater gain in waist circumference, compared with those in the lowest quintile.
“Associations with dissimilarity scores are consistent with evidence from feeding studies showing that exposure to foods with different characteristics led to increased energy intake, which may partially explain gain in waist circumference over time,” wrote Marcia C. de Oliveira Otto, PhD, from the University of Texas Health Science Centre at Houston and coauthors.
The same was seen in short-term interventional studies, where most showed that having access to a wider variety of foods actually led to an increase in intake, compared with being served only a single food.
For example, one study showed adults offered a second course of sandwiches with different fillings to the first course actually ate 30% more than those served the same option for both courses.
Another study randomized overweight and obese adults to an unlimited number of snack options consumed less than once a day, or any amount of one favored snack option, with all snacks being within a daily caloric goal. This study found that, over the course of 8 weeks, participants offered a variety of snacks ate 25% more servings than those with the one snack type.
The authors suggested that variety amplifies sensory stimulation and decreases satiety.
“Although calorie restriction goals were achieved in both groups, a significant increase in sensory-specific satiety and monotony ratings over time was observed in participants assigned to the one-snack option but not in participants assigned to a variety of snacks,” they wrote.
The relationship between dietary diversity and dietary quality is also complex. Investigators for a cross-sectional study in China found less-than-optimal consumption of the nine food groups in the Chinese dietary guidelines – in particular, fruits, vegetables, fish, and dairy – in diets with higher diversity scores.
“Overall, limited evidence shows no benefit to diet quality or diet healthfulness associated with increased food count or with a more even distribution of energy across foods, whereas findings from one observational study suggest that greater dissimilarity in foods consumed may be inversely associated with a healthy eating pattern.”
In conclusion, the advisory committee said that it was more appropriate to promote a healthy eating pattern, emphasizing intake of plant foods, protein sources, low-fat dairy, vegetable oils, and nuts.
One author declared research funding from the Hass Avocado Board. No other relevant conflicts of interest were declared.
SOURCE: de Oliveira Otto MC et al. Circulation. 2018 Aug. 9. doi: 10.1161/CIR.0000000000000595.
FROM CIRCULATION
Key clinical point: Dietary variety may not reflect healthiness or dietary quality.
Major finding: A varied diet is associated with higher intake and poorer quality.
Study details: Literature review and science advisory from the American Heart Association.
Disclosures: One author declared research funding from the Hass Avocado Board. No other relevant conflicts of interest were declared.
Source: de Oliveira Otto MC et al. Circulation. 2018 Aug. 9. doi: 10.1161/CIR.0000000000000595.
In Memoriam: Dr. John Ochsner
John Lockwood Ochsner, MD, (1927-2018), a world-renowned heart surgeon, will be remembered as a charismatic and skilled surgeon, a dedicated teacher, a loving father, and a role model for the hundreds of surgeons he trained.
Dr. Ochsner was born in 1927 in Madison, Wisc., but was raised in New Orleans. and received his medical degree from Tulane University. He started his surgical residency at the University of Michigan but was drafted into military service during the Korean War. He then completed his residency at Baylor University and received his cardiac training under Michael DeBakey. MD,. Dr. DeBakey was a close family friend who had studied under John’s father at Tulane and had worked in the original Ochsner Clinic. John was very close to Dr. DeBakey, who was also John’s babysitter in early life.
Dr. John, as he was known, grew up in shadow of giants, including his father, Alton, who founded the Ochsner Clinic, and Michael DeBakey who was a protégé of Alton. As John was finishing his training with Dr. DeBakey he was asked to stay on in Houston as a member of Dr. DeBakey’s team. The Ochsner Clinic was expanding rapidly in New Orleans, however, and everyone was desirous of having John return. John initially planned to stay with Dr. DeBakey until the director of the Ochsner Clinic flew to Houston to meet with John to convince him to return to New Orleans. His argument was, “John, you will be a great surgeon wherever you practice, but there is only one hospital that has your name on the front of it!” John returned to the Ochsner Clinic in 1961, where he spent the next 57 years.
John Ochsner was revered as an innovative, energetic and talented surgeon, performing over 12,000 operations, including the first cardiac transplant in the Gulf South. He always said he was happiest in the operating room, and loved teaching young resident surgeons. He believed that “surgery is an art as much as a science. ... You have to improvise almost every case -- no two cases are the same - and that’s where the fun of surgery comes in, making something new that particular moment that you’ve never seen before. ... It’s like opening up a package; it’s always a little different.”
He authored more than 300 peer-reviewed publications and gave innumerable scientific lectures around the world. He served as President of the International Society for Cardiovascular Surgery as well as the American Association for Thoracic Surgery. Over his career, he was elected president of more than 10 medical associations.
John, like his father, was active in many aspects of New Orleans life. He was an avid golfer and tennis player, and was always ready with a joke. He lived life with humor and enthusiasm, and was a member of multiple social clubs, developing lifelong friends from around the world. He was particularly thrilled when he was chosen as Rex, King of Carnival, in 1990, following in the royal footsteps of his father, who was King of Rex in 1948. Both of his granddaughters were presented as Maids of the Rex organization.
John is survived by his wife of over 64 years, Mary Lou Ochsner; a sister, Isabel Mann: two sons, Dr. John Ochsner, Jr., and Frank Ochsner, and two daughters, Joby Ochsner and Dr. Katherine Isabel Ochsner; he has two grandchildren.
Larry H. Hollier, MD, Professor of Surgery, Chancellor, Louisiana State University Health Science Center at New Orleans
John Lockwood Ochsner, MD, (1927-2018), a world-renowned heart surgeon, will be remembered as a charismatic and skilled surgeon, a dedicated teacher, a loving father, and a role model for the hundreds of surgeons he trained.
Dr. Ochsner was born in 1927 in Madison, Wisc., but was raised in New Orleans. and received his medical degree from Tulane University. He started his surgical residency at the University of Michigan but was drafted into military service during the Korean War. He then completed his residency at Baylor University and received his cardiac training under Michael DeBakey. MD,. Dr. DeBakey was a close family friend who had studied under John’s father at Tulane and had worked in the original Ochsner Clinic. John was very close to Dr. DeBakey, who was also John’s babysitter in early life.
Dr. John, as he was known, grew up in shadow of giants, including his father, Alton, who founded the Ochsner Clinic, and Michael DeBakey who was a protégé of Alton. As John was finishing his training with Dr. DeBakey he was asked to stay on in Houston as a member of Dr. DeBakey’s team. The Ochsner Clinic was expanding rapidly in New Orleans, however, and everyone was desirous of having John return. John initially planned to stay with Dr. DeBakey until the director of the Ochsner Clinic flew to Houston to meet with John to convince him to return to New Orleans. His argument was, “John, you will be a great surgeon wherever you practice, but there is only one hospital that has your name on the front of it!” John returned to the Ochsner Clinic in 1961, where he spent the next 57 years.
John Ochsner was revered as an innovative, energetic and talented surgeon, performing over 12,000 operations, including the first cardiac transplant in the Gulf South. He always said he was happiest in the operating room, and loved teaching young resident surgeons. He believed that “surgery is an art as much as a science. ... You have to improvise almost every case -- no two cases are the same - and that’s where the fun of surgery comes in, making something new that particular moment that you’ve never seen before. ... It’s like opening up a package; it’s always a little different.”
He authored more than 300 peer-reviewed publications and gave innumerable scientific lectures around the world. He served as President of the International Society for Cardiovascular Surgery as well as the American Association for Thoracic Surgery. Over his career, he was elected president of more than 10 medical associations.
John, like his father, was active in many aspects of New Orleans life. He was an avid golfer and tennis player, and was always ready with a joke. He lived life with humor and enthusiasm, and was a member of multiple social clubs, developing lifelong friends from around the world. He was particularly thrilled when he was chosen as Rex, King of Carnival, in 1990, following in the royal footsteps of his father, who was King of Rex in 1948. Both of his granddaughters were presented as Maids of the Rex organization.
John is survived by his wife of over 64 years, Mary Lou Ochsner; a sister, Isabel Mann: two sons, Dr. John Ochsner, Jr., and Frank Ochsner, and two daughters, Joby Ochsner and Dr. Katherine Isabel Ochsner; he has two grandchildren.
Larry H. Hollier, MD, Professor of Surgery, Chancellor, Louisiana State University Health Science Center at New Orleans
John Lockwood Ochsner, MD, (1927-2018), a world-renowned heart surgeon, will be remembered as a charismatic and skilled surgeon, a dedicated teacher, a loving father, and a role model for the hundreds of surgeons he trained.
Dr. Ochsner was born in 1927 in Madison, Wisc., but was raised in New Orleans. and received his medical degree from Tulane University. He started his surgical residency at the University of Michigan but was drafted into military service during the Korean War. He then completed his residency at Baylor University and received his cardiac training under Michael DeBakey. MD,. Dr. DeBakey was a close family friend who had studied under John’s father at Tulane and had worked in the original Ochsner Clinic. John was very close to Dr. DeBakey, who was also John’s babysitter in early life.
Dr. John, as he was known, grew up in shadow of giants, including his father, Alton, who founded the Ochsner Clinic, and Michael DeBakey who was a protégé of Alton. As John was finishing his training with Dr. DeBakey he was asked to stay on in Houston as a member of Dr. DeBakey’s team. The Ochsner Clinic was expanding rapidly in New Orleans, however, and everyone was desirous of having John return. John initially planned to stay with Dr. DeBakey until the director of the Ochsner Clinic flew to Houston to meet with John to convince him to return to New Orleans. His argument was, “John, you will be a great surgeon wherever you practice, but there is only one hospital that has your name on the front of it!” John returned to the Ochsner Clinic in 1961, where he spent the next 57 years.
John Ochsner was revered as an innovative, energetic and talented surgeon, performing over 12,000 operations, including the first cardiac transplant in the Gulf South. He always said he was happiest in the operating room, and loved teaching young resident surgeons. He believed that “surgery is an art as much as a science. ... You have to improvise almost every case -- no two cases are the same - and that’s where the fun of surgery comes in, making something new that particular moment that you’ve never seen before. ... It’s like opening up a package; it’s always a little different.”
He authored more than 300 peer-reviewed publications and gave innumerable scientific lectures around the world. He served as President of the International Society for Cardiovascular Surgery as well as the American Association for Thoracic Surgery. Over his career, he was elected president of more than 10 medical associations.
John, like his father, was active in many aspects of New Orleans life. He was an avid golfer and tennis player, and was always ready with a joke. He lived life with humor and enthusiasm, and was a member of multiple social clubs, developing lifelong friends from around the world. He was particularly thrilled when he was chosen as Rex, King of Carnival, in 1990, following in the royal footsteps of his father, who was King of Rex in 1948. Both of his granddaughters were presented as Maids of the Rex organization.
John is survived by his wife of over 64 years, Mary Lou Ochsner; a sister, Isabel Mann: two sons, Dr. John Ochsner, Jr., and Frank Ochsner, and two daughters, Joby Ochsner and Dr. Katherine Isabel Ochsner; he has two grandchildren.
Larry H. Hollier, MD, Professor of Surgery, Chancellor, Louisiana State University Health Science Center at New Orleans
I want you to do my job
It is never easy to replace a legend. The Vascular Specialist that Russell Samson has left behind does not require saving. There are, however, problems ahead for all vascular surgeons, and my hope is to use this forum to unite us. Vascular surgery is a small specialty in an existential crisis. There are just over 3,000 of us in the United States. Think of Vascular Specialist as your hometown newspaper. Instead of high school sports and bake sales we will cover scientific meetings, clinical trials, and relevant legislation. And maybe the occasional swap meet.
Different points of view are going to be an essential part of this process. Russell Samson represented the posh, privileged world of private practice while I come from the rough and tumble streets of academia (just checking to see if he is still reading). My hope is to bring more. More Tips and Tricks, more Point/Counterpoint, more Letters to the Editor, more input from you.
How can you get involved? If you read something and have a response, send it to me. Volunteer to write up a technical tip or provide a medical debate. Have an idea for a guest editorial? Let me know, preferably before you write it. If it is good I will likely publish it. If not, well we can still be friends. Keep in mind, unlike book publishing, we work on strict deadlines. (To the three people I owe book chapters: Soon, I promise!) We will also be starting a vascular news section for brief committee updates, course registration openings, and relevant policy changes.
Vascular Specialist is now open for submissions. Contact us at [email protected].
It is never easy to replace a legend. The Vascular Specialist that Russell Samson has left behind does not require saving. There are, however, problems ahead for all vascular surgeons, and my hope is to use this forum to unite us. Vascular surgery is a small specialty in an existential crisis. There are just over 3,000 of us in the United States. Think of Vascular Specialist as your hometown newspaper. Instead of high school sports and bake sales we will cover scientific meetings, clinical trials, and relevant legislation. And maybe the occasional swap meet.
Different points of view are going to be an essential part of this process. Russell Samson represented the posh, privileged world of private practice while I come from the rough and tumble streets of academia (just checking to see if he is still reading). My hope is to bring more. More Tips and Tricks, more Point/Counterpoint, more Letters to the Editor, more input from you.
How can you get involved? If you read something and have a response, send it to me. Volunteer to write up a technical tip or provide a medical debate. Have an idea for a guest editorial? Let me know, preferably before you write it. If it is good I will likely publish it. If not, well we can still be friends. Keep in mind, unlike book publishing, we work on strict deadlines. (To the three people I owe book chapters: Soon, I promise!) We will also be starting a vascular news section for brief committee updates, course registration openings, and relevant policy changes.
Vascular Specialist is now open for submissions. Contact us at [email protected].
It is never easy to replace a legend. The Vascular Specialist that Russell Samson has left behind does not require saving. There are, however, problems ahead for all vascular surgeons, and my hope is to use this forum to unite us. Vascular surgery is a small specialty in an existential crisis. There are just over 3,000 of us in the United States. Think of Vascular Specialist as your hometown newspaper. Instead of high school sports and bake sales we will cover scientific meetings, clinical trials, and relevant legislation. And maybe the occasional swap meet.
Different points of view are going to be an essential part of this process. Russell Samson represented the posh, privileged world of private practice while I come from the rough and tumble streets of academia (just checking to see if he is still reading). My hope is to bring more. More Tips and Tricks, more Point/Counterpoint, more Letters to the Editor, more input from you.
How can you get involved? If you read something and have a response, send it to me. Volunteer to write up a technical tip or provide a medical debate. Have an idea for a guest editorial? Let me know, preferably before you write it. If it is good I will likely publish it. If not, well we can still be friends. Keep in mind, unlike book publishing, we work on strict deadlines. (To the three people I owe book chapters: Soon, I promise!) We will also be starting a vascular news section for brief committee updates, course registration openings, and relevant policy changes.
Vascular Specialist is now open for submissions. Contact us at [email protected].
Get up to Speed with VESAP4
With certification exams coming up, some surgeons may want to brush up.
The Vascular Educational Self-Assessment Program (VESAP), fourth edition, is a great study tool. As with previous editions, VESAP4 contains 10 topic sections, each with dozens of study and test questions, with 550 questions overall. VESAP4 offers both learning and testing modes, plus both Continuing Medical Education and Maintenance of Certification self-assessment credits. This edition also includes a mobile app (Apple products only) for off-line study. The program can be purchased as a comprehensive package or by individual modules. Package cost is $549 for members, $449 for candidates and $649 for non-members. Module pricing is $75, $65 and $85 per module, respectively.
With certification exams coming up, some surgeons may want to brush up.
The Vascular Educational Self-Assessment Program (VESAP), fourth edition, is a great study tool. As with previous editions, VESAP4 contains 10 topic sections, each with dozens of study and test questions, with 550 questions overall. VESAP4 offers both learning and testing modes, plus both Continuing Medical Education and Maintenance of Certification self-assessment credits. This edition also includes a mobile app (Apple products only) for off-line study. The program can be purchased as a comprehensive package or by individual modules. Package cost is $549 for members, $449 for candidates and $649 for non-members. Module pricing is $75, $65 and $85 per module, respectively.
With certification exams coming up, some surgeons may want to brush up.
The Vascular Educational Self-Assessment Program (VESAP), fourth edition, is a great study tool. As with previous editions, VESAP4 contains 10 topic sections, each with dozens of study and test questions, with 550 questions overall. VESAP4 offers both learning and testing modes, plus both Continuing Medical Education and Maintenance of Certification self-assessment credits. This edition also includes a mobile app (Apple products only) for off-line study. The program can be purchased as a comprehensive package or by individual modules. Package cost is $549 for members, $449 for candidates and $649 for non-members. Module pricing is $75, $65 and $85 per module, respectively.
Familial risk of myeloid malignancies
A large study has revealed “the strongest evidence yet” supporting genetic susceptibility to myeloid malignancies, according to a researcher.
The study showed that first-degree relatives of patients with myeloid malignancies had double the risk of developing a myeloid malignancy themselves, when compared to the general population.
The researchers observed significant risks for developing acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), essential thrombocythemia (ET), and polycythemia vera (PV).
“Our study provides the strongest evidence yet for inherited risk for these diseases—evidence that has proved evasive before, in part, because these cancers are relatively uncommon, and our ability to characterize these diseases has, until recently, been limited,” said Amit Sud, MBChB, PhD, of The Institute of Cancer Research in London, UK.
Dr Sud and his colleagues described their research in a letter to Blood.
The researchers analyzed data from the Swedish Family-Cancer Database, which included 93,199 first-degree relatives of 35,037 patients with myeloid malignancies. The patients had been diagnosed between 1958 and 2015.
First-degree relatives of the patients had an increased risk of all myeloid malignancies, with a standardized incidence ratio (SIR) of 1.99 (95% CI 1.12-2.04).
For individual diseases, there was a significant association between family history and increased risk for:
- AML—SIR=1.53 (95% CI 1.21-2.17)
- ET—SIR=6.30 (95% CI 3.95-9.54)
- MDS—SIR=6.87 (95% CI 4.07-10.86)
- PV—SIR=7.66 (95% CI 5.74-10.02).
Dr Sud and his colleagues noted that the strongest familial relative risks tended to occur for the same disease, but there were significant associations between different myeloid malignancies as well.
Risk by age group
The researchers also looked at familial relative risk for the same disease by patients’ age at diagnosis and observed a significantly increased risk for younger cases for all myeloproliferative neoplasms (MPNs) combined, PV, and MDS.
The SIRs for MPNs were 6.46 (95% CI 5.12-8.04) for patients age 59 or younger and 4.15 (95% CI 3.38-5.04) for patients older than 59.
The SIRs for PV were 10.90 (95% CI 7.12-15.97) for patients age 59 or younger and 5.96 (95% CI 3.93-8.67) for patients older than 59.
The SIRs for MDS were 11.95 (95% CI 6.36-20.43) for patients age 68 or younger and 3.27 (95% CI 1.06-7.63) for patients older than 68.
Risk by number of relatives
Dr Sud and his colleagues also discovered that familial relative risks of all myeloid malignancies and MPNs were significantly associated with the number of first-degree relatives affected by myeloid malignancies or MPNs.
The SIRs for first-degree relatives with 2 or more affected relatives were 4.55 (95% CI 2.08-8.64) for all myeloid malignancies and 17.82 (95% CI 5.79-24.89) for MPNs.
The SIRs for first-degree relatives with 1 affected relative were 1.96 (95% CI 1.79-2.15) for all myeloid malignancies and 4.83 (95% CI 4.14-5.60) for MPNs.
The researchers said these results suggest inherited genetic changes increase the risk of myeloid malignancies, although environmental factors shared in families could also play a role.
“In the future, our findings could help identify people at higher risk than normal because of their family background who could be prioritized for medical help like screening to catch the disease earlier if it arises,” Dr Sud said.
This study was funded by German Cancer Aid, the Swedish Research Council, ALF funding from Region Skåne, DKFZ, and Bloodwise.
A large study has revealed “the strongest evidence yet” supporting genetic susceptibility to myeloid malignancies, according to a researcher.
The study showed that first-degree relatives of patients with myeloid malignancies had double the risk of developing a myeloid malignancy themselves, when compared to the general population.
The researchers observed significant risks for developing acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), essential thrombocythemia (ET), and polycythemia vera (PV).
“Our study provides the strongest evidence yet for inherited risk for these diseases—evidence that has proved evasive before, in part, because these cancers are relatively uncommon, and our ability to characterize these diseases has, until recently, been limited,” said Amit Sud, MBChB, PhD, of The Institute of Cancer Research in London, UK.
Dr Sud and his colleagues described their research in a letter to Blood.
The researchers analyzed data from the Swedish Family-Cancer Database, which included 93,199 first-degree relatives of 35,037 patients with myeloid malignancies. The patients had been diagnosed between 1958 and 2015.
First-degree relatives of the patients had an increased risk of all myeloid malignancies, with a standardized incidence ratio (SIR) of 1.99 (95% CI 1.12-2.04).
For individual diseases, there was a significant association between family history and increased risk for:
- AML—SIR=1.53 (95% CI 1.21-2.17)
- ET—SIR=6.30 (95% CI 3.95-9.54)
- MDS—SIR=6.87 (95% CI 4.07-10.86)
- PV—SIR=7.66 (95% CI 5.74-10.02).
Dr Sud and his colleagues noted that the strongest familial relative risks tended to occur for the same disease, but there were significant associations between different myeloid malignancies as well.
Risk by age group
The researchers also looked at familial relative risk for the same disease by patients’ age at diagnosis and observed a significantly increased risk for younger cases for all myeloproliferative neoplasms (MPNs) combined, PV, and MDS.
The SIRs for MPNs were 6.46 (95% CI 5.12-8.04) for patients age 59 or younger and 4.15 (95% CI 3.38-5.04) for patients older than 59.
The SIRs for PV were 10.90 (95% CI 7.12-15.97) for patients age 59 or younger and 5.96 (95% CI 3.93-8.67) for patients older than 59.
The SIRs for MDS were 11.95 (95% CI 6.36-20.43) for patients age 68 or younger and 3.27 (95% CI 1.06-7.63) for patients older than 68.
Risk by number of relatives
Dr Sud and his colleagues also discovered that familial relative risks of all myeloid malignancies and MPNs were significantly associated with the number of first-degree relatives affected by myeloid malignancies or MPNs.
The SIRs for first-degree relatives with 2 or more affected relatives were 4.55 (95% CI 2.08-8.64) for all myeloid malignancies and 17.82 (95% CI 5.79-24.89) for MPNs.
The SIRs for first-degree relatives with 1 affected relative were 1.96 (95% CI 1.79-2.15) for all myeloid malignancies and 4.83 (95% CI 4.14-5.60) for MPNs.
The researchers said these results suggest inherited genetic changes increase the risk of myeloid malignancies, although environmental factors shared in families could also play a role.
“In the future, our findings could help identify people at higher risk than normal because of their family background who could be prioritized for medical help like screening to catch the disease earlier if it arises,” Dr Sud said.
This study was funded by German Cancer Aid, the Swedish Research Council, ALF funding from Region Skåne, DKFZ, and Bloodwise.
A large study has revealed “the strongest evidence yet” supporting genetic susceptibility to myeloid malignancies, according to a researcher.
The study showed that first-degree relatives of patients with myeloid malignancies had double the risk of developing a myeloid malignancy themselves, when compared to the general population.
The researchers observed significant risks for developing acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), essential thrombocythemia (ET), and polycythemia vera (PV).
“Our study provides the strongest evidence yet for inherited risk for these diseases—evidence that has proved evasive before, in part, because these cancers are relatively uncommon, and our ability to characterize these diseases has, until recently, been limited,” said Amit Sud, MBChB, PhD, of The Institute of Cancer Research in London, UK.
Dr Sud and his colleagues described their research in a letter to Blood.
The researchers analyzed data from the Swedish Family-Cancer Database, which included 93,199 first-degree relatives of 35,037 patients with myeloid malignancies. The patients had been diagnosed between 1958 and 2015.
First-degree relatives of the patients had an increased risk of all myeloid malignancies, with a standardized incidence ratio (SIR) of 1.99 (95% CI 1.12-2.04).
For individual diseases, there was a significant association between family history and increased risk for:
- AML—SIR=1.53 (95% CI 1.21-2.17)
- ET—SIR=6.30 (95% CI 3.95-9.54)
- MDS—SIR=6.87 (95% CI 4.07-10.86)
- PV—SIR=7.66 (95% CI 5.74-10.02).
Dr Sud and his colleagues noted that the strongest familial relative risks tended to occur for the same disease, but there were significant associations between different myeloid malignancies as well.
Risk by age group
The researchers also looked at familial relative risk for the same disease by patients’ age at diagnosis and observed a significantly increased risk for younger cases for all myeloproliferative neoplasms (MPNs) combined, PV, and MDS.
The SIRs for MPNs were 6.46 (95% CI 5.12-8.04) for patients age 59 or younger and 4.15 (95% CI 3.38-5.04) for patients older than 59.
The SIRs for PV were 10.90 (95% CI 7.12-15.97) for patients age 59 or younger and 5.96 (95% CI 3.93-8.67) for patients older than 59.
The SIRs for MDS were 11.95 (95% CI 6.36-20.43) for patients age 68 or younger and 3.27 (95% CI 1.06-7.63) for patients older than 68.
Risk by number of relatives
Dr Sud and his colleagues also discovered that familial relative risks of all myeloid malignancies and MPNs were significantly associated with the number of first-degree relatives affected by myeloid malignancies or MPNs.
The SIRs for first-degree relatives with 2 or more affected relatives were 4.55 (95% CI 2.08-8.64) for all myeloid malignancies and 17.82 (95% CI 5.79-24.89) for MPNs.
The SIRs for first-degree relatives with 1 affected relative were 1.96 (95% CI 1.79-2.15) for all myeloid malignancies and 4.83 (95% CI 4.14-5.60) for MPNs.
The researchers said these results suggest inherited genetic changes increase the risk of myeloid malignancies, although environmental factors shared in families could also play a role.
“In the future, our findings could help identify people at higher risk than normal because of their family background who could be prioritized for medical help like screening to catch the disease earlier if it arises,” Dr Sud said.
This study was funded by German Cancer Aid, the Swedish Research Council, ALF funding from Region Skåne, DKFZ, and Bloodwise.
Man, 25, With Sinus Pain, Sore Throat, and Rash
A 25-year-old white man presents to urgent care with a nine-day history of increasing sinus pressure, mild sore throat, dry cough, and low-grade fever. Physical exam of the ears, nose, throat, and chest is unremarkable, but the patient does display mild maxillary sinus tenderness. Sinus pain (and symptom duration) is the primary complaint. The patient was recently exposed to influenza B, but a rapid flu test is negative. A five-day course of amoxicillin-clavulanate is prescribed for a presumed diagnosis of bacterial sinusitis.
One week later, the patient returns with worsening sore throat and a morbilliform rash (see Figures 1 and 2), which covers the trunk, upper arms, and thighs. He has no known allergies to drugs, foods, or other environmental triggers. Examination reveals slightly tender, mobile anterior and posterior cervical lymphadenopathy, as well as bilateral tonsillar erythema and exudates, which were not present at the initial visit.
The rest of the exam is normal, and the patient’s sinus symptoms have resolved. Heterophile antibody testing yields positive results, suggesting infection with Epstein-Barr virus (EBV).
DISCUSSION
EBV is a pervasive herpesvirus that infects approximately 95% of adults worldwide.1 More than 90% of adults are seropositive for EBV antibodies by the age of 30.2 Although affected individuals are often asymptomatic, some patients develop symptoms of infectious mononucleosis (IM).2 An aminopenicillin rash can occur in patients with IM who are treated with amoxicillin or ampicillin, as was the case with this patient.
Incidence and pathophysiology
Infection with EBV most commonly occurs between the ages of 15 and 24.1,2 Infection before the age of 1 is rarely seen due to circulating maternal antibodies; incidence of IM in those younger than 1 or older than 30 is < 1 per 1,000 cases annually.2 The average annual incidence of infection is 0.5% in young adults (ages 15 and 24) but has been reported as high as 4.8%.2 About 10% to 20% of people who never knowingly come into contact with the virus will become infected annually; of those, up to 50% will develop IM.2 There are no known correlations in incidence based on sex or seasonal changes.2
Like all herpesviridae, EBV causes a latent infection that persists for a lifetime, specifically in replicating B lymphocytes.1 Saliva is the most common mode of EBV transmission, as viral shedding occurs in the throat and mouth.1,3 While the viral load in saliva is the highest during the first six months of infection, there are no clear data determining the risk for transmission throughout the course of asymptomatic shedding.4 There is a 30-to-50–day incubation period of EBV infection before a patient experiences symptoms of IM.1 During this period, B lymphocytes and epithelial cells (specifically in the tonsillar crypts) are believed to be the source of viral replication.1,3
Clinical presentation of IM
Common symptoms of IM include sore throat, fever, and fatigue. Approximately one in 13 patients ages 16 to 20 who present with a fever and sore throat will be diagnosed with IM.6 However, symptomatology alone is more sensitive than specific and is not sufficient to diagnose IM.6 Combined fatigue and pharyngitis is sensitive (81%-83%) but not specific, and posterior cervical lymphadenopathy increases the likelihood of IM (specificity, 87%).6
Continue to: The classic triad associated with IM includes...
The classic triad associated with IM includes fever, pharyngitis, and cervical lymphadenopathy, with morbilliform rash and palatal petechiae appearing less commonly (3%-15% and 25%, respectively).1,2,9 In affected patients, a transient truncal rash manifests within the first few days of disease onset.7 Tonsillar enlargement is also a common, but not specific, sign of acute IM.2 Splenomegaly is found in 15% to 65% of patients, typically developing within three weeks of disease onset.1,5,9
Hematologic complications occur in 25% to 50% of cases.5 Mild thrombocytopenia is common; however, more severe complications—such as hemolytic anemia, hemolytic-uremic syndrome, aplastic anemia, and disseminated intravascular coagulation—have also been associated with IM.5 Fulminant and potentially fatal complications are more common in immunocompromised patients.1,2
Pediatric and geriatric patients (those older than 65) may present with atypical signs and symptoms. For example, children are commonly asymptomatic or may present with a nonspecific viral illness.1 In addition, pediatric and elderly populations can develop elevated aminotransferase levels, and 26% of elderly patients present with jaundice (compared with 8% of young adults).2,3,7
Workup/differential diagnosis
Heterophile antibody testing is the most efficient and least expensive diagnostic test to confirm IM (sensitivity, 63%-84%; specificity, 84%-100%).2 Within the first week of IM, however, 25% of patients will produce a false-negative antibody test; a complete blood count (CBC) with differential and peripheral smear are appropriate follow-up tests.1,2,5 Detecting 10% or more atypical lymphocytes on a peripheral smear has a specificity of 95% and sensitivity of 61.3% for detecting IM, and a CBC with a lymphocyte count of less than 4,000 mm has a 99% negative predictive value.2 Viral capsid IgM testing can confirm the diagnosis of IM in an unclear clinical situation, such as a negative heterophile antibody test with an absolute lymphocyte count > 4,000 mm or in which 10% or more atypical lymphocytes were detected.2
Pharyngitis is caused by group A streptococci in 15% to 30% of children and 10% of adults worldwide, and 30% of patients with IM have a concomitant infection with group A streptococci.1,5 Because pharyngitis is a common presenting symptom of IM, rapid antigen strep test is appropriate when working up these patients.2 In addition, HIV, cytomegalovirus, human herpesvirus-6, and Toxoplasma gondii should be considered in the differential for patients with pharyngitis, fatigue, malaise, and lymphadenopathy—especially if the group A streptococci/EBV workup is negative.1,2,5
Continue to: EBV is also a known trigger of...
EBV is also a known trigger of hemophagocytic lymphohistocytosis (HLH). In a Japanese study, half of all HLH cases correlated with a primary infection of EBV.2,3,8 EBV is also the first confirmed oncogenic virus.3 EBV DNA in the plasma is now a tumor marker for nasopharyngeal carcinoma (sensitivity, 96%; specificity, 93%).8 Hodgkin lymphoma tumors are associated with EBV infection in 50% of cases.4 However, EBV seropositivity is ubiquitous (approximately 95%), while these correlated conditions are relatively uncommon; patient education on these issues is therefore not needed.
Treatment/complications
Aminopenicillin rash classically occurs in patients with IM who are treated with amoxicillin or ampicillin. These antibiotics are most commonly prescribed for suspected group A streptococci infection.7 Up to 95% of patients with IM who are exposed to these drugs develop this rash within two to 10 days of receiving the first dose of the antibiotic.9,10 Similar eruptions are often reported following administration of other penicillins, but not with the same frequency seen with ampicillin or amoxicillin (see Table 1).11
The mechanism of the aminopenicillin rash is not completely understood, but one theory is that the activated CD8+ cells react with the drug antigens and deposit in the skin.10 Another proposed mechanism is that antigens formed against activated polyclonal B cells create immune complexes with the drug, which then deposit in the skin.10
No known factors increase the incidence of this rash in patients after antibiotic exposure (eg, previous penicillin exposure, antibiotic dose or duration, patient age or ethnicity, atopic history).7 The rash generally resolves within a week after antibiotic discontinuation.7 Importantly, the development of a rash in a patient with EBV after administration of an aminopenicillin is not associated with an allergy nor is it a sign of an unfavorable reaction to such drugs in the future.12
The rash can be described as morbilliform or scarlatiniform and should be distinguished from the rash that acute IM can cause. Five percent of patients with an aminopenicillin rash will have an urticarial presentation, whereas 95% of patients have an exanthematous presentation.1,9,10 Although it can be quite difficult to distinguish one rash from the other, the aminopenicillin rash is more widespread than that associated with acute IM, covering extensor surfaces and spreading to the face, trunk, neck, mucous membranes, and sometimes the palms and soles.1,7,9,10 The rash caused by IM begins within the first few days of disease, whereas the aminopenicillin rash will manifest seven to 10 days after antibiotic exposure and is commonly pruritic.1 Each rash will last about one week.1
Continue to: CONCLUSION
CONCLUSION
The diagnosis of EBV can be challenging due to its similarity to group A streptococcal pharyngitis and other viral syndromes. In this case, the development of classic symptoms, along with the morbilliform eruption following administration of an aminopenicillin, was strongly suggestive of this diagnosis. This pairing of EBV infection and aminopenicillin rash does not indicate a penicillin allergy.
1. Hall LD, Eminger LA, Hesterman KS, Heymann WR. Epstein-Barr virus: dermatologic associations and implications. J Am Acad Dermatol. 2015;72(1):1-19.
2. Womack J, Jimenez M. Common questions about infectious mononucleosis. Am Fam Physician. 2015;91(6): 372-376.
3. Tangye SG, Palendira U, Edwards ES. Human immunity against EBV—lessons from the clinic. J Exp Med. 2017; 214(2):269-283.
4. Guidry JT, Birdwell CE, Scott RS. Epstein-Barr virus in the pathogenesis of oral cancers. Oral Dis. 2018;24:497-508.
5. Ebell MH, Call M, Shinholser J, Gardner J. Does this patient have infectious mononucleosis? The rational clinical examination systematic review. JAMA. 2016; 315(14):1502-1509.
6. Lernia VD, Mansouri Y. Epstein-Barr virus and skin manifestations in childhood. Int J Dermatol. 2013;52(10):1177-1184.
7. Luzuriaga K, Sullivan JL. Infectious mononucleosis. N Engl J Med. 2010;362:1993-2000.
8. Chovel-Sella A, Ben Tov A, Lahav A, et al. Incidence of rash after amoxicillin treatment in children with infectious mononucleosis. Pediatrics. 2013;131(5):e1424-e1427.
9. Chan KCA, Woo JKS, King A, et al. Analysis of plasma Epstein-Barr virus DNA to screen for nasopharyngeal cancer. N Engl J Med. 2017;377:513-522.
10. Forgie SED, Marrie TJ. Cutaneous eruptions associated with antimicrobials in patients with infectious mononucleosis. Am J Med. 2015;128(1):e1-e2.
11. Haverkos HW, Amsel Z, Drotman DP. Adverse virus-drug interactions. Rev Infect Dis. 1991;13(4):697-704.
12. Nazareth I, Mortimer P, McKendrick GD. Ampicillin sensitivity in infectious mononucleosis: temporary or permanent? Scand J Infect Dis. 1972;4(3):229-230.
A 25-year-old white man presents to urgent care with a nine-day history of increasing sinus pressure, mild sore throat, dry cough, and low-grade fever. Physical exam of the ears, nose, throat, and chest is unremarkable, but the patient does display mild maxillary sinus tenderness. Sinus pain (and symptom duration) is the primary complaint. The patient was recently exposed to influenza B, but a rapid flu test is negative. A five-day course of amoxicillin-clavulanate is prescribed for a presumed diagnosis of bacterial sinusitis.
One week later, the patient returns with worsening sore throat and a morbilliform rash (see Figures 1 and 2), which covers the trunk, upper arms, and thighs. He has no known allergies to drugs, foods, or other environmental triggers. Examination reveals slightly tender, mobile anterior and posterior cervical lymphadenopathy, as well as bilateral tonsillar erythema and exudates, which were not present at the initial visit.
The rest of the exam is normal, and the patient’s sinus symptoms have resolved. Heterophile antibody testing yields positive results, suggesting infection with Epstein-Barr virus (EBV).
DISCUSSION
EBV is a pervasive herpesvirus that infects approximately 95% of adults worldwide.1 More than 90% of adults are seropositive for EBV antibodies by the age of 30.2 Although affected individuals are often asymptomatic, some patients develop symptoms of infectious mononucleosis (IM).2 An aminopenicillin rash can occur in patients with IM who are treated with amoxicillin or ampicillin, as was the case with this patient.
Incidence and pathophysiology
Infection with EBV most commonly occurs between the ages of 15 and 24.1,2 Infection before the age of 1 is rarely seen due to circulating maternal antibodies; incidence of IM in those younger than 1 or older than 30 is < 1 per 1,000 cases annually.2 The average annual incidence of infection is 0.5% in young adults (ages 15 and 24) but has been reported as high as 4.8%.2 About 10% to 20% of people who never knowingly come into contact with the virus will become infected annually; of those, up to 50% will develop IM.2 There are no known correlations in incidence based on sex or seasonal changes.2
Like all herpesviridae, EBV causes a latent infection that persists for a lifetime, specifically in replicating B lymphocytes.1 Saliva is the most common mode of EBV transmission, as viral shedding occurs in the throat and mouth.1,3 While the viral load in saliva is the highest during the first six months of infection, there are no clear data determining the risk for transmission throughout the course of asymptomatic shedding.4 There is a 30-to-50–day incubation period of EBV infection before a patient experiences symptoms of IM.1 During this period, B lymphocytes and epithelial cells (specifically in the tonsillar crypts) are believed to be the source of viral replication.1,3
Clinical presentation of IM
Common symptoms of IM include sore throat, fever, and fatigue. Approximately one in 13 patients ages 16 to 20 who present with a fever and sore throat will be diagnosed with IM.6 However, symptomatology alone is more sensitive than specific and is not sufficient to diagnose IM.6 Combined fatigue and pharyngitis is sensitive (81%-83%) but not specific, and posterior cervical lymphadenopathy increases the likelihood of IM (specificity, 87%).6
Continue to: The classic triad associated with IM includes...
The classic triad associated with IM includes fever, pharyngitis, and cervical lymphadenopathy, with morbilliform rash and palatal petechiae appearing less commonly (3%-15% and 25%, respectively).1,2,9 In affected patients, a transient truncal rash manifests within the first few days of disease onset.7 Tonsillar enlargement is also a common, but not specific, sign of acute IM.2 Splenomegaly is found in 15% to 65% of patients, typically developing within three weeks of disease onset.1,5,9
Hematologic complications occur in 25% to 50% of cases.5 Mild thrombocytopenia is common; however, more severe complications—such as hemolytic anemia, hemolytic-uremic syndrome, aplastic anemia, and disseminated intravascular coagulation—have also been associated with IM.5 Fulminant and potentially fatal complications are more common in immunocompromised patients.1,2
Pediatric and geriatric patients (those older than 65) may present with atypical signs and symptoms. For example, children are commonly asymptomatic or may present with a nonspecific viral illness.1 In addition, pediatric and elderly populations can develop elevated aminotransferase levels, and 26% of elderly patients present with jaundice (compared with 8% of young adults).2,3,7
Workup/differential diagnosis
Heterophile antibody testing is the most efficient and least expensive diagnostic test to confirm IM (sensitivity, 63%-84%; specificity, 84%-100%).2 Within the first week of IM, however, 25% of patients will produce a false-negative antibody test; a complete blood count (CBC) with differential and peripheral smear are appropriate follow-up tests.1,2,5 Detecting 10% or more atypical lymphocytes on a peripheral smear has a specificity of 95% and sensitivity of 61.3% for detecting IM, and a CBC with a lymphocyte count of less than 4,000 mm has a 99% negative predictive value.2 Viral capsid IgM testing can confirm the diagnosis of IM in an unclear clinical situation, such as a negative heterophile antibody test with an absolute lymphocyte count > 4,000 mm or in which 10% or more atypical lymphocytes were detected.2
Pharyngitis is caused by group A streptococci in 15% to 30% of children and 10% of adults worldwide, and 30% of patients with IM have a concomitant infection with group A streptococci.1,5 Because pharyngitis is a common presenting symptom of IM, rapid antigen strep test is appropriate when working up these patients.2 In addition, HIV, cytomegalovirus, human herpesvirus-6, and Toxoplasma gondii should be considered in the differential for patients with pharyngitis, fatigue, malaise, and lymphadenopathy—especially if the group A streptococci/EBV workup is negative.1,2,5
Continue to: EBV is also a known trigger of...
EBV is also a known trigger of hemophagocytic lymphohistocytosis (HLH). In a Japanese study, half of all HLH cases correlated with a primary infection of EBV.2,3,8 EBV is also the first confirmed oncogenic virus.3 EBV DNA in the plasma is now a tumor marker for nasopharyngeal carcinoma (sensitivity, 96%; specificity, 93%).8 Hodgkin lymphoma tumors are associated with EBV infection in 50% of cases.4 However, EBV seropositivity is ubiquitous (approximately 95%), while these correlated conditions are relatively uncommon; patient education on these issues is therefore not needed.
Treatment/complications
Aminopenicillin rash classically occurs in patients with IM who are treated with amoxicillin or ampicillin. These antibiotics are most commonly prescribed for suspected group A streptococci infection.7 Up to 95% of patients with IM who are exposed to these drugs develop this rash within two to 10 days of receiving the first dose of the antibiotic.9,10 Similar eruptions are often reported following administration of other penicillins, but not with the same frequency seen with ampicillin or amoxicillin (see Table 1).11
The mechanism of the aminopenicillin rash is not completely understood, but one theory is that the activated CD8+ cells react with the drug antigens and deposit in the skin.10 Another proposed mechanism is that antigens formed against activated polyclonal B cells create immune complexes with the drug, which then deposit in the skin.10
No known factors increase the incidence of this rash in patients after antibiotic exposure (eg, previous penicillin exposure, antibiotic dose or duration, patient age or ethnicity, atopic history).7 The rash generally resolves within a week after antibiotic discontinuation.7 Importantly, the development of a rash in a patient with EBV after administration of an aminopenicillin is not associated with an allergy nor is it a sign of an unfavorable reaction to such drugs in the future.12
The rash can be described as morbilliform or scarlatiniform and should be distinguished from the rash that acute IM can cause. Five percent of patients with an aminopenicillin rash will have an urticarial presentation, whereas 95% of patients have an exanthematous presentation.1,9,10 Although it can be quite difficult to distinguish one rash from the other, the aminopenicillin rash is more widespread than that associated with acute IM, covering extensor surfaces and spreading to the face, trunk, neck, mucous membranes, and sometimes the palms and soles.1,7,9,10 The rash caused by IM begins within the first few days of disease, whereas the aminopenicillin rash will manifest seven to 10 days after antibiotic exposure and is commonly pruritic.1 Each rash will last about one week.1
Continue to: CONCLUSION
CONCLUSION
The diagnosis of EBV can be challenging due to its similarity to group A streptococcal pharyngitis and other viral syndromes. In this case, the development of classic symptoms, along with the morbilliform eruption following administration of an aminopenicillin, was strongly suggestive of this diagnosis. This pairing of EBV infection and aminopenicillin rash does not indicate a penicillin allergy.
A 25-year-old white man presents to urgent care with a nine-day history of increasing sinus pressure, mild sore throat, dry cough, and low-grade fever. Physical exam of the ears, nose, throat, and chest is unremarkable, but the patient does display mild maxillary sinus tenderness. Sinus pain (and symptom duration) is the primary complaint. The patient was recently exposed to influenza B, but a rapid flu test is negative. A five-day course of amoxicillin-clavulanate is prescribed for a presumed diagnosis of bacterial sinusitis.
One week later, the patient returns with worsening sore throat and a morbilliform rash (see Figures 1 and 2), which covers the trunk, upper arms, and thighs. He has no known allergies to drugs, foods, or other environmental triggers. Examination reveals slightly tender, mobile anterior and posterior cervical lymphadenopathy, as well as bilateral tonsillar erythema and exudates, which were not present at the initial visit.
The rest of the exam is normal, and the patient’s sinus symptoms have resolved. Heterophile antibody testing yields positive results, suggesting infection with Epstein-Barr virus (EBV).
DISCUSSION
EBV is a pervasive herpesvirus that infects approximately 95% of adults worldwide.1 More than 90% of adults are seropositive for EBV antibodies by the age of 30.2 Although affected individuals are often asymptomatic, some patients develop symptoms of infectious mononucleosis (IM).2 An aminopenicillin rash can occur in patients with IM who are treated with amoxicillin or ampicillin, as was the case with this patient.
Incidence and pathophysiology
Infection with EBV most commonly occurs between the ages of 15 and 24.1,2 Infection before the age of 1 is rarely seen due to circulating maternal antibodies; incidence of IM in those younger than 1 or older than 30 is < 1 per 1,000 cases annually.2 The average annual incidence of infection is 0.5% in young adults (ages 15 and 24) but has been reported as high as 4.8%.2 About 10% to 20% of people who never knowingly come into contact with the virus will become infected annually; of those, up to 50% will develop IM.2 There are no known correlations in incidence based on sex or seasonal changes.2
Like all herpesviridae, EBV causes a latent infection that persists for a lifetime, specifically in replicating B lymphocytes.1 Saliva is the most common mode of EBV transmission, as viral shedding occurs in the throat and mouth.1,3 While the viral load in saliva is the highest during the first six months of infection, there are no clear data determining the risk for transmission throughout the course of asymptomatic shedding.4 There is a 30-to-50–day incubation period of EBV infection before a patient experiences symptoms of IM.1 During this period, B lymphocytes and epithelial cells (specifically in the tonsillar crypts) are believed to be the source of viral replication.1,3
Clinical presentation of IM
Common symptoms of IM include sore throat, fever, and fatigue. Approximately one in 13 patients ages 16 to 20 who present with a fever and sore throat will be diagnosed with IM.6 However, symptomatology alone is more sensitive than specific and is not sufficient to diagnose IM.6 Combined fatigue and pharyngitis is sensitive (81%-83%) but not specific, and posterior cervical lymphadenopathy increases the likelihood of IM (specificity, 87%).6
Continue to: The classic triad associated with IM includes...
The classic triad associated with IM includes fever, pharyngitis, and cervical lymphadenopathy, with morbilliform rash and palatal petechiae appearing less commonly (3%-15% and 25%, respectively).1,2,9 In affected patients, a transient truncal rash manifests within the first few days of disease onset.7 Tonsillar enlargement is also a common, but not specific, sign of acute IM.2 Splenomegaly is found in 15% to 65% of patients, typically developing within three weeks of disease onset.1,5,9
Hematologic complications occur in 25% to 50% of cases.5 Mild thrombocytopenia is common; however, more severe complications—such as hemolytic anemia, hemolytic-uremic syndrome, aplastic anemia, and disseminated intravascular coagulation—have also been associated with IM.5 Fulminant and potentially fatal complications are more common in immunocompromised patients.1,2
Pediatric and geriatric patients (those older than 65) may present with atypical signs and symptoms. For example, children are commonly asymptomatic or may present with a nonspecific viral illness.1 In addition, pediatric and elderly populations can develop elevated aminotransferase levels, and 26% of elderly patients present with jaundice (compared with 8% of young adults).2,3,7
Workup/differential diagnosis
Heterophile antibody testing is the most efficient and least expensive diagnostic test to confirm IM (sensitivity, 63%-84%; specificity, 84%-100%).2 Within the first week of IM, however, 25% of patients will produce a false-negative antibody test; a complete blood count (CBC) with differential and peripheral smear are appropriate follow-up tests.1,2,5 Detecting 10% or more atypical lymphocytes on a peripheral smear has a specificity of 95% and sensitivity of 61.3% for detecting IM, and a CBC with a lymphocyte count of less than 4,000 mm has a 99% negative predictive value.2 Viral capsid IgM testing can confirm the diagnosis of IM in an unclear clinical situation, such as a negative heterophile antibody test with an absolute lymphocyte count > 4,000 mm or in which 10% or more atypical lymphocytes were detected.2
Pharyngitis is caused by group A streptococci in 15% to 30% of children and 10% of adults worldwide, and 30% of patients with IM have a concomitant infection with group A streptococci.1,5 Because pharyngitis is a common presenting symptom of IM, rapid antigen strep test is appropriate when working up these patients.2 In addition, HIV, cytomegalovirus, human herpesvirus-6, and Toxoplasma gondii should be considered in the differential for patients with pharyngitis, fatigue, malaise, and lymphadenopathy—especially if the group A streptococci/EBV workup is negative.1,2,5
Continue to: EBV is also a known trigger of...
EBV is also a known trigger of hemophagocytic lymphohistocytosis (HLH). In a Japanese study, half of all HLH cases correlated with a primary infection of EBV.2,3,8 EBV is also the first confirmed oncogenic virus.3 EBV DNA in the plasma is now a tumor marker for nasopharyngeal carcinoma (sensitivity, 96%; specificity, 93%).8 Hodgkin lymphoma tumors are associated with EBV infection in 50% of cases.4 However, EBV seropositivity is ubiquitous (approximately 95%), while these correlated conditions are relatively uncommon; patient education on these issues is therefore not needed.
Treatment/complications
Aminopenicillin rash classically occurs in patients with IM who are treated with amoxicillin or ampicillin. These antibiotics are most commonly prescribed for suspected group A streptococci infection.7 Up to 95% of patients with IM who are exposed to these drugs develop this rash within two to 10 days of receiving the first dose of the antibiotic.9,10 Similar eruptions are often reported following administration of other penicillins, but not with the same frequency seen with ampicillin or amoxicillin (see Table 1).11
The mechanism of the aminopenicillin rash is not completely understood, but one theory is that the activated CD8+ cells react with the drug antigens and deposit in the skin.10 Another proposed mechanism is that antigens formed against activated polyclonal B cells create immune complexes with the drug, which then deposit in the skin.10
No known factors increase the incidence of this rash in patients after antibiotic exposure (eg, previous penicillin exposure, antibiotic dose or duration, patient age or ethnicity, atopic history).7 The rash generally resolves within a week after antibiotic discontinuation.7 Importantly, the development of a rash in a patient with EBV after administration of an aminopenicillin is not associated with an allergy nor is it a sign of an unfavorable reaction to such drugs in the future.12
The rash can be described as morbilliform or scarlatiniform and should be distinguished from the rash that acute IM can cause. Five percent of patients with an aminopenicillin rash will have an urticarial presentation, whereas 95% of patients have an exanthematous presentation.1,9,10 Although it can be quite difficult to distinguish one rash from the other, the aminopenicillin rash is more widespread than that associated with acute IM, covering extensor surfaces and spreading to the face, trunk, neck, mucous membranes, and sometimes the palms and soles.1,7,9,10 The rash caused by IM begins within the first few days of disease, whereas the aminopenicillin rash will manifest seven to 10 days after antibiotic exposure and is commonly pruritic.1 Each rash will last about one week.1
Continue to: CONCLUSION
CONCLUSION
The diagnosis of EBV can be challenging due to its similarity to group A streptococcal pharyngitis and other viral syndromes. In this case, the development of classic symptoms, along with the morbilliform eruption following administration of an aminopenicillin, was strongly suggestive of this diagnosis. This pairing of EBV infection and aminopenicillin rash does not indicate a penicillin allergy.
1. Hall LD, Eminger LA, Hesterman KS, Heymann WR. Epstein-Barr virus: dermatologic associations and implications. J Am Acad Dermatol. 2015;72(1):1-19.
2. Womack J, Jimenez M. Common questions about infectious mononucleosis. Am Fam Physician. 2015;91(6): 372-376.
3. Tangye SG, Palendira U, Edwards ES. Human immunity against EBV—lessons from the clinic. J Exp Med. 2017; 214(2):269-283.
4. Guidry JT, Birdwell CE, Scott RS. Epstein-Barr virus in the pathogenesis of oral cancers. Oral Dis. 2018;24:497-508.
5. Ebell MH, Call M, Shinholser J, Gardner J. Does this patient have infectious mononucleosis? The rational clinical examination systematic review. JAMA. 2016; 315(14):1502-1509.
6. Lernia VD, Mansouri Y. Epstein-Barr virus and skin manifestations in childhood. Int J Dermatol. 2013;52(10):1177-1184.
7. Luzuriaga K, Sullivan JL. Infectious mononucleosis. N Engl J Med. 2010;362:1993-2000.
8. Chovel-Sella A, Ben Tov A, Lahav A, et al. Incidence of rash after amoxicillin treatment in children with infectious mononucleosis. Pediatrics. 2013;131(5):e1424-e1427.
9. Chan KCA, Woo JKS, King A, et al. Analysis of plasma Epstein-Barr virus DNA to screen for nasopharyngeal cancer. N Engl J Med. 2017;377:513-522.
10. Forgie SED, Marrie TJ. Cutaneous eruptions associated with antimicrobials in patients with infectious mononucleosis. Am J Med. 2015;128(1):e1-e2.
11. Haverkos HW, Amsel Z, Drotman DP. Adverse virus-drug interactions. Rev Infect Dis. 1991;13(4):697-704.
12. Nazareth I, Mortimer P, McKendrick GD. Ampicillin sensitivity in infectious mononucleosis: temporary or permanent? Scand J Infect Dis. 1972;4(3):229-230.
1. Hall LD, Eminger LA, Hesterman KS, Heymann WR. Epstein-Barr virus: dermatologic associations and implications. J Am Acad Dermatol. 2015;72(1):1-19.
2. Womack J, Jimenez M. Common questions about infectious mononucleosis. Am Fam Physician. 2015;91(6): 372-376.
3. Tangye SG, Palendira U, Edwards ES. Human immunity against EBV—lessons from the clinic. J Exp Med. 2017; 214(2):269-283.
4. Guidry JT, Birdwell CE, Scott RS. Epstein-Barr virus in the pathogenesis of oral cancers. Oral Dis. 2018;24:497-508.
5. Ebell MH, Call M, Shinholser J, Gardner J. Does this patient have infectious mononucleosis? The rational clinical examination systematic review. JAMA. 2016; 315(14):1502-1509.
6. Lernia VD, Mansouri Y. Epstein-Barr virus and skin manifestations in childhood. Int J Dermatol. 2013;52(10):1177-1184.
7. Luzuriaga K, Sullivan JL. Infectious mononucleosis. N Engl J Med. 2010;362:1993-2000.
8. Chovel-Sella A, Ben Tov A, Lahav A, et al. Incidence of rash after amoxicillin treatment in children with infectious mononucleosis. Pediatrics. 2013;131(5):e1424-e1427.
9. Chan KCA, Woo JKS, King A, et al. Analysis of plasma Epstein-Barr virus DNA to screen for nasopharyngeal cancer. N Engl J Med. 2017;377:513-522.
10. Forgie SED, Marrie TJ. Cutaneous eruptions associated with antimicrobials in patients with infectious mononucleosis. Am J Med. 2015;128(1):e1-e2.
11. Haverkos HW, Amsel Z, Drotman DP. Adverse virus-drug interactions. Rev Infect Dis. 1991;13(4):697-704.
12. Nazareth I, Mortimer P, McKendrick GD. Ampicillin sensitivity in infectious mononucleosis: temporary or permanent? Scand J Infect Dis. 1972;4(3):229-230.
