Doctor with a clipboard

A survey of nearly 700 US physicians revealed that many do not know the basic requirements for a drug to receive approval from the US Food and

Drug Administration (FDA).

The results also suggested that most physicians don’t understand the FDA’s “breakthrough therapy” designation.

Since 2012, the FDA has been able to designate a drug as a breakthrough therapy if preliminary clinical evidence suggests it provides an advantage

over existing options.

Aaron S. Kesselheim, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues wanted to determine how much physicians understood about this designation and if they had a basic understanding of the FDA’s requirements for drug approval.

So the researchers surveyed internists and specialists from the American Board of Internal Medicine’s diplomate list and reported the results of this survey in JAMA.

Of the 1148 physicians contacted, 692 (60%) responded. Participants were asked 3 questions about FDA approval and 5 about breakthrough therapies.

FDA approval

Seventy-three percent of respondents incorrectly believed that, for a drug to gain FDA approval, it must be as effective as drugs that are already approved.

However, 85% of respondents answered correctly that FDA-approved drugs typically have a favorable benefit/harm ratio.

Seventy percent of respondents incorrectly believed that FDA approval requires a drug to have both a statistically significant and a clinically important effect.

Only 6% of respondents knew the correct answer—that neither is required.

Breakthrough designation

Twenty percent of respondents said they were “familiar” (17%) or “very familiar” (3%) with breakthrough therapy designation, while 37% said they were “a little familiar,” and 42% said they were “not familiar at all.”

Fifty-eight percent of respondents said they were “fairly certain” that an FDA-approved breakthrough drug represents a major advance over currently approved treatments for its indication. Thirty-one percent said they were “fairly uncertain,” 5% said they were “very uncertain,” and 6% said they were “very certain.”

Fifty-two percent of respondents incorrectly believed that strong evidence (ie, randomized trials) is needed to earn the breakthrough designation.

However, 45% correctly answered that only preliminary evidence (eg, uncontrolled studies or studies testing surrogate outcomes) is needed. Four percent said very preliminary evidence (eg, in vitro laboratory or animal studies) is needed.

Seventy-seven percent of respondents incorrectly believed that, when the FDA grants breakthrough designation, there is high-quality evidence that the drug is more effective than currently approved treatments.

But 74% of respondents answered correctly that breakthrough designation does not mean there is high-quality evidence that the drug is safer than currently approved treatments.

Dr Kesselheim and his colleagues said the misconceptions identified in this survey may lead physicians to overprescribe newly approved drugs—particularly breakthrough therapies—and inadequately communicate how well these drugs work to patients.

Doctor with a clipboard

A survey of nearly 700 US physicians revealed that many do not know the basic requirements for a drug to receive approval from the US Food and

Drug Administration (FDA).

The results also suggested that most physicians don’t understand the FDA’s “breakthrough therapy” designation.

Since 2012, the FDA has been able to designate a drug as a breakthrough therapy if preliminary clinical evidence suggests it provides an advantage

over existing options.

Aaron S. Kesselheim, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues wanted to determine how much physicians understood about this designation and if they had a basic understanding of the FDA’s requirements for drug approval.

So the researchers surveyed internists and specialists from the American Board of Internal Medicine’s diplomate list and reported the results of this survey in JAMA.

Of the 1148 physicians contacted, 692 (60%) responded. Participants were asked 3 questions about FDA approval and 5 about breakthrough therapies.

FDA approval

Seventy-three percent of respondents incorrectly believed that, for a drug to gain FDA approval, it must be as effective as drugs that are already approved.

However, 85% of respondents answered correctly that FDA-approved drugs typically have a favorable benefit/harm ratio.

Seventy percent of respondents incorrectly believed that FDA approval requires a drug to have both a statistically significant and a clinically important effect.

Only 6% of respondents knew the correct answer—that neither is required.

Breakthrough designation

Twenty percent of respondents said they were “familiar” (17%) or “very familiar” (3%) with breakthrough therapy designation, while 37% said they were “a little familiar,” and 42% said they were “not familiar at all.”

Fifty-eight percent of respondents said they were “fairly certain” that an FDA-approved breakthrough drug represents a major advance over currently approved treatments for its indication. Thirty-one percent said they were “fairly uncertain,” 5% said they were “very uncertain,” and 6% said they were “very certain.”

Fifty-two percent of respondents incorrectly believed that strong evidence (ie, randomized trials) is needed to earn the breakthrough designation.

However, 45% correctly answered that only preliminary evidence (eg, uncontrolled studies or studies testing surrogate outcomes) is needed. Four percent said very preliminary evidence (eg, in vitro laboratory or animal studies) is needed.

Seventy-seven percent of respondents incorrectly believed that, when the FDA grants breakthrough designation, there is high-quality evidence that the drug is more effective than currently approved treatments.

But 74% of respondents answered correctly that breakthrough designation does not mean there is high-quality evidence that the drug is safer than currently approved treatments.

Dr Kesselheim and his colleagues said the misconceptions identified in this survey may lead physicians to overprescribe newly approved drugs—particularly breakthrough therapies—and inadequately communicate how well these drugs work to patients.

Doctor with a clipboard

A survey of nearly 700 US physicians revealed that many do not know the basic requirements for a drug to receive approval from the US Food and

Drug Administration (FDA).

The results also suggested that most physicians don’t understand the FDA’s “breakthrough therapy” designation.

Since 2012, the FDA has been able to designate a drug as a breakthrough therapy if preliminary clinical evidence suggests it provides an advantage

over existing options.

Aaron S. Kesselheim, MD, of Brigham and Women’s Hospital in Boston, Massachusetts, and his colleagues wanted to determine how much physicians understood about this designation and if they had a basic understanding of the FDA’s requirements for drug approval.

So the researchers surveyed internists and specialists from the American Board of Internal Medicine’s diplomate list and reported the results of this survey in JAMA.

Of the 1148 physicians contacted, 692 (60%) responded. Participants were asked 3 questions about FDA approval and 5 about breakthrough therapies.

FDA approval

Seventy-three percent of respondents incorrectly believed that, for a drug to gain FDA approval, it must be as effective as drugs that are already approved.

However, 85% of respondents answered correctly that FDA-approved drugs typically have a favorable benefit/harm ratio.

Seventy percent of respondents incorrectly believed that FDA approval requires a drug to have both a statistically significant and a clinically important effect.

Only 6% of respondents knew the correct answer—that neither is required.

Breakthrough designation

Twenty percent of respondents said they were “familiar” (17%) or “very familiar” (3%) with breakthrough therapy designation, while 37% said they were “a little familiar,” and 42% said they were “not familiar at all.”

Fifty-eight percent of respondents said they were “fairly certain” that an FDA-approved breakthrough drug represents a major advance over currently approved treatments for its indication. Thirty-one percent said they were “fairly uncertain,” 5% said they were “very uncertain,” and 6% said they were “very certain.”

Fifty-two percent of respondents incorrectly believed that strong evidence (ie, randomized trials) is needed to earn the breakthrough designation.

However, 45% correctly answered that only preliminary evidence (eg, uncontrolled studies or studies testing surrogate outcomes) is needed. Four percent said very preliminary evidence (eg, in vitro laboratory or animal studies) is needed.

Seventy-seven percent of respondents incorrectly believed that, when the FDA grants breakthrough designation, there is high-quality evidence that the drug is more effective than currently approved treatments.

But 74% of respondents answered correctly that breakthrough designation does not mean there is high-quality evidence that the drug is safer than currently approved treatments.

Dr Kesselheim and his colleagues said the misconceptions identified in this survey may lead physicians to overprescribe newly approved drugs—particularly breakthrough therapies—and inadequately communicate how well these drugs work to patients.

Blood for transfusion

Photo by Elise Amendola

Certain methods of manufacturing red cell concentrates (RCCs) may be less damaging than others, according to research published in Vox Sanguinis.

The study showed that damage-associated molecular patterns (DAMPs) in stored blood differ according to the process and materials used to collect or prepare RCCs for transfusion.

Researchers believe this discovery could help reduce adverse reactions in transfusion recipients and potentially impact how blood is collected around the world.

To conduct this study, the researchers compared RCCs collected at blood donation centers in the US and Canada. The team examined the influence of manufacturing methods on the levels of mitochondrial (mt) DNA and extracellular vesicle (EV) DAMPs in RCCs.

“Working with the American team at Blood Systems Research Institute was key to this research because of the wide variations in blood manufacturing processes present in the US,” said Jason Acker, PhD, of Canadian Blood Services’ Centre for Innovation in Edmonton, Alberta.

“In countries like Canada, where there is a national blood service, manufacturing methods are largely standardized, so it is difficult to compare various methods. But blood collection in the US is characterized by dozens of independent blood centers that use a variety of available manufacturing processes. The Americans provided the variations we needed to measure red cell damage and to ascertain whether it can be attributed to different manufacturing methods.”

Manufacturing methods

The researchers evaluated 87 RCCs prepared using 9 different methods, outlined in the following table.

Results

For all RCCs, the researchers assessed the levels of mtDNA and the number and cell of origin of EVs on storage days 5 and 42.

They observed a 100-fold difference in mtDNA levels between the different methods.

The highest mtDNA levels were in the non-leukoreduced RCCs, followed by the MCS+ and Trima apheresis RCCs. The mean levels were 5.3 x 10⁵ copies/µL, 1.3 x 10⁵ copies/µL, and 1.2 x 10⁵ copies/µL, respectively.

The lowest mtDNA levels were seen with the semi-automated methods. The mean levels ranged from 3.8 x 10³ copies/µL to 5.9 x 10³ copies/µL.

The researchers also saw a 10-fold difference in EV levels between the different methods.

The team detected red blood cell-derived CD235a+ EVs in fresh RCCs, which increased in most RCCs over the storage period (but not for FenBC and MCS+).

Platelet-derived CD41a+ EVs were highest in non-leukoreduced and Trima RCCs and did not change significantly during storage.

White blood cell-derived CD11b+ and CD66b+ EVs were low in most RCCs (though not in Trima and FenMAN-non-LR RCCs), and their levels did not significantly change during storage.

White blood cell-derived CD14+ EVs were negligible in fresh RCCs but increased in several RCCs during storage (FenMAN, Alyx, MCS+, and Trima).

Next steps

“There must be more testing of the apheresis collections equipment, blood bags, leukoreduction filters, and other variations in manufacturing methods to determine what single element or combination of elements in the various red blood cell manufacturing processes result in high levels of DAMPs and why,” said Michael Busch, MD, PhD, of Blood Systems Research Institute in San Francisco, California.

“We also need to understand how mitochondrial DAMPs are involved in adverse reactions to red blood cell transfusions,” added Sonia Bakkour, PhD, also from Blood Systems Research Institute.

“Some recently published studies on platelet components link high levels of mitochondrial DAMPs to adverse transfusion reactions. We need to see if DAMPs have similar adverse effects on recipients of red blood cell transfusions.”

“We think that our research could lead to finding the best way to manufacture red blood cells,” Dr Acker noted.

“It’s clear now that manufacturing methods matter. We . . . are keen to explore what’s in the blood bag or in the filters or in the tubing, for example, that can be minimized or eliminated, improving the outcome in patients who receive blood transfusions.”

Blood for transfusion

Photo by Elise Amendola

Certain methods of manufacturing red cell concentrates (RCCs) may be less damaging than others, according to research published in Vox Sanguinis.

The study showed that damage-associated molecular patterns (DAMPs) in stored blood differ according to the process and materials used to collect or prepare RCCs for transfusion.

Researchers believe this discovery could help reduce adverse reactions in transfusion recipients and potentially impact how blood is collected around the world.

To conduct this study, the researchers compared RCCs collected at blood donation centers in the US and Canada. The team examined the influence of manufacturing methods on the levels of mitochondrial (mt) DNA and extracellular vesicle (EV) DAMPs in RCCs.

“Working with the American team at Blood Systems Research Institute was key to this research because of the wide variations in blood manufacturing processes present in the US,” said Jason Acker, PhD, of Canadian Blood Services’ Centre for Innovation in Edmonton, Alberta.

“In countries like Canada, where there is a national blood service, manufacturing methods are largely standardized, so it is difficult to compare various methods. But blood collection in the US is characterized by dozens of independent blood centers that use a variety of available manufacturing processes. The Americans provided the variations we needed to measure red cell damage and to ascertain whether it can be attributed to different manufacturing methods.”

Manufacturing methods

The researchers evaluated 87 RCCs prepared using 9 different methods, outlined in the following table.

Results

For all RCCs, the researchers assessed the levels of mtDNA and the number and cell of origin of EVs on storage days 5 and 42.

They observed a 100-fold difference in mtDNA levels between the different methods.

The highest mtDNA levels were in the non-leukoreduced RCCs, followed by the MCS+ and Trima apheresis RCCs. The mean levels were 5.3 x 10⁵ copies/µL, 1.3 x 10⁵ copies/µL, and 1.2 x 10⁵ copies/µL, respectively.

The lowest mtDNA levels were seen with the semi-automated methods. The mean levels ranged from 3.8 x 10³ copies/µL to 5.9 x 10³ copies/µL.

The researchers also saw a 10-fold difference in EV levels between the different methods.

The team detected red blood cell-derived CD235a+ EVs in fresh RCCs, which increased in most RCCs over the storage period (but not for FenBC and MCS+).

Platelet-derived CD41a+ EVs were highest in non-leukoreduced and Trima RCCs and did not change significantly during storage.

White blood cell-derived CD11b+ and CD66b+ EVs were low in most RCCs (though not in Trima and FenMAN-non-LR RCCs), and their levels did not significantly change during storage.

White blood cell-derived CD14+ EVs were negligible in fresh RCCs but increased in several RCCs during storage (FenMAN, Alyx, MCS+, and Trima).

Next steps

“There must be more testing of the apheresis collections equipment, blood bags, leukoreduction filters, and other variations in manufacturing methods to determine what single element or combination of elements in the various red blood cell manufacturing processes result in high levels of DAMPs and why,” said Michael Busch, MD, PhD, of Blood Systems Research Institute in San Francisco, California.

“We also need to understand how mitochondrial DAMPs are involved in adverse reactions to red blood cell transfusions,” added Sonia Bakkour, PhD, also from Blood Systems Research Institute.

“Some recently published studies on platelet components link high levels of mitochondrial DAMPs to adverse transfusion reactions. We need to see if DAMPs have similar adverse effects on recipients of red blood cell transfusions.”

“We think that our research could lead to finding the best way to manufacture red blood cells,” Dr Acker noted.

“It’s clear now that manufacturing methods matter. We . . . are keen to explore what’s in the blood bag or in the filters or in the tubing, for example, that can be minimized or eliminated, improving the outcome in patients who receive blood transfusions.”

Blood for transfusion

Photo by Elise Amendola

Certain methods of manufacturing red cell concentrates (RCCs) may be less damaging than others, according to research published in Vox Sanguinis.

The study showed that damage-associated molecular patterns (DAMPs) in stored blood differ according to the process and materials used to collect or prepare RCCs for transfusion.

Researchers believe this discovery could help reduce adverse reactions in transfusion recipients and potentially impact how blood is collected around the world.

To conduct this study, the researchers compared RCCs collected at blood donation centers in the US and Canada. The team examined the influence of manufacturing methods on the levels of mitochondrial (mt) DNA and extracellular vesicle (EV) DAMPs in RCCs.

“Working with the American team at Blood Systems Research Institute was key to this research because of the wide variations in blood manufacturing processes present in the US,” said Jason Acker, PhD, of Canadian Blood Services’ Centre for Innovation in Edmonton, Alberta.

“In countries like Canada, where there is a national blood service, manufacturing methods are largely standardized, so it is difficult to compare various methods. But blood collection in the US is characterized by dozens of independent blood centers that use a variety of available manufacturing processes. The Americans provided the variations we needed to measure red cell damage and to ascertain whether it can be attributed to different manufacturing methods.”

Manufacturing methods

The researchers evaluated 87 RCCs prepared using 9 different methods, outlined in the following table.

Results

For all RCCs, the researchers assessed the levels of mtDNA and the number and cell of origin of EVs on storage days 5 and 42.

They observed a 100-fold difference in mtDNA levels between the different methods.

The highest mtDNA levels were in the non-leukoreduced RCCs, followed by the MCS+ and Trima apheresis RCCs. The mean levels were 5.3 x 10⁵ copies/µL, 1.3 x 10⁵ copies/µL, and 1.2 x 10⁵ copies/µL, respectively.

The lowest mtDNA levels were seen with the semi-automated methods. The mean levels ranged from 3.8 x 10³ copies/µL to 5.9 x 10³ copies/µL.

The researchers also saw a 10-fold difference in EV levels between the different methods.

The team detected red blood cell-derived CD235a+ EVs in fresh RCCs, which increased in most RCCs over the storage period (but not for FenBC and MCS+).

Platelet-derived CD41a+ EVs were highest in non-leukoreduced and Trima RCCs and did not change significantly during storage.

White blood cell-derived CD11b+ and CD66b+ EVs were low in most RCCs (though not in Trima and FenMAN-non-LR RCCs), and their levels did not significantly change during storage.

White blood cell-derived CD14+ EVs were negligible in fresh RCCs but increased in several RCCs during storage (FenMAN, Alyx, MCS+, and Trima).

Next steps

“There must be more testing of the apheresis collections equipment, blood bags, leukoreduction filters, and other variations in manufacturing methods to determine what single element or combination of elements in the various red blood cell manufacturing processes result in high levels of DAMPs and why,” said Michael Busch, MD, PhD, of Blood Systems Research Institute in San Francisco, California.

“We also need to understand how mitochondrial DAMPs are involved in adverse reactions to red blood cell transfusions,” added Sonia Bakkour, PhD, also from Blood Systems Research Institute.

“Some recently published studies on platelet components link high levels of mitochondrial DAMPs to adverse transfusion reactions. We need to see if DAMPs have similar adverse effects on recipients of red blood cell transfusions.”

“We think that our research could lead to finding the best way to manufacture red blood cells,” Dr Acker noted.

“It’s clear now that manufacturing methods matter. We . . . are keen to explore what’s in the blood bag or in the filters or in the tubing, for example, that can be minimized or eliminated, improving the outcome in patients who receive blood transfusions.”

Continuity of care for the 18-year-old male who told Dr. Lillian M. Beard about his depression requires collaboration with colleagues, but coordinating that care takes resources. Who is in charge of ensuring care?

“This is where teams come in,” says Dr. April Barbour, associate professor of medicine and chief of general internal medicine George Washington University, Washington. “Because it doesn’t necessarily need to be the psychiatrist. A discharge coordinator could serve that role and send that information back.”

“I agree. And then we come back to the next thing: Who’s going to pay for the team? Who’s going to manage the team? Also, the other thing – with any team, someone’s got to be the quarterback – someone has to make sure or verify that it happened,” says Dr. Lorenzo Norris, cohost of Mental Health Consult, and assistant professor of psychiatry and behavioral sciences at George Washington University.

“When you are treating mental illness, you need a team-based approach so that you can look at everything that is going on. If you are strictly algorithmic based, there are going to be fatal errors,” Dr. Norris says. “It doesn’t reduce down to that level.”

Continuity of care for the 18-year-old male who told Dr. Lillian M. Beard about his depression requires collaboration with colleagues, but coordinating that care takes resources. Who is in charge of ensuring care?

“This is where teams come in,” says Dr. April Barbour, associate professor of medicine and chief of general internal medicine George Washington University, Washington. “Because it doesn’t necessarily need to be the psychiatrist. A discharge coordinator could serve that role and send that information back.”

“I agree. And then we come back to the next thing: Who’s going to pay for the team? Who’s going to manage the team? Also, the other thing – with any team, someone’s got to be the quarterback – someone has to make sure or verify that it happened,” says Dr. Lorenzo Norris, cohost of Mental Health Consult, and assistant professor of psychiatry and behavioral sciences at George Washington University.

“When you are treating mental illness, you need a team-based approach so that you can look at everything that is going on. If you are strictly algorithmic based, there are going to be fatal errors,” Dr. Norris says. “It doesn’t reduce down to that level.”

Continuity of care for the 18-year-old male who told Dr. Lillian M. Beard about his depression requires collaboration with colleagues, but coordinating that care takes resources. Who is in charge of ensuring care?

“This is where teams come in,” says Dr. April Barbour, associate professor of medicine and chief of general internal medicine George Washington University, Washington. “Because it doesn’t necessarily need to be the psychiatrist. A discharge coordinator could serve that role and send that information back.”

“I agree. And then we come back to the next thing: Who’s going to pay for the team? Who’s going to manage the team? Also, the other thing – with any team, someone’s got to be the quarterback – someone has to make sure or verify that it happened,” says Dr. Lorenzo Norris, cohost of Mental Health Consult, and assistant professor of psychiatry and behavioral sciences at George Washington University.

“When you are treating mental illness, you need a team-based approach so that you can look at everything that is going on. If you are strictly algorithmic based, there are going to be fatal errors,” Dr. Norris says. “It doesn’t reduce down to that level.”

When a patient presents with depression, how is it possible to determine whether serious mental illnesses such as first-episode psychosis are unfolding? In this video, Dr. Lillian M. Beard, who practices pediatrics in Silver Spring, Md., discusses the case of an 18-year-old male with thoughts of suicide whose situation was exacerbated by poor continuity of care.

“From the crisis center, [the patient] was admitted to a hospital, but there wasn’t a follow-up,” Dr. Beard says.

This discussion between Dr. Beard; Dr. Lorenzo Norris, cohost of Mental Health Consult and medical director of psychiatric and behavioral services at George Washington University Hospital, Washington; and Dr. David Pickar, adjunct professor of psychiatry at Johns Hopkins University, Baltimore, explores how these kinds of circumstances might affect the patient’s case, as well as other clinical considerations that should help guide referral.

When a patient presents with depression, how is it possible to determine whether serious mental illnesses such as first-episode psychosis are unfolding? In this video, Dr. Lillian M. Beard, who practices pediatrics in Silver Spring, Md., discusses the case of an 18-year-old male with thoughts of suicide whose situation was exacerbated by poor continuity of care.

“From the crisis center, [the patient] was admitted to a hospital, but there wasn’t a follow-up,” Dr. Beard says.

This discussion between Dr. Beard; Dr. Lorenzo Norris, cohost of Mental Health Consult and medical director of psychiatric and behavioral services at George Washington University Hospital, Washington; and Dr. David Pickar, adjunct professor of psychiatry at Johns Hopkins University, Baltimore, explores how these kinds of circumstances might affect the patient’s case, as well as other clinical considerations that should help guide referral.

When a patient presents with depression, how is it possible to determine whether serious mental illnesses such as first-episode psychosis are unfolding? In this video, Dr. Lillian M. Beard, who practices pediatrics in Silver Spring, Md., discusses the case of an 18-year-old male with thoughts of suicide whose situation was exacerbated by poor continuity of care.

“From the crisis center, [the patient] was admitted to a hospital, but there wasn’t a follow-up,” Dr. Beard says.

This discussion between Dr. Beard; Dr. Lorenzo Norris, cohost of Mental Health Consult and medical director of psychiatric and behavioral services at George Washington University Hospital, Washington; and Dr. David Pickar, adjunct professor of psychiatry at Johns Hopkins University, Baltimore, explores how these kinds of circumstances might affect the patient’s case, as well as other clinical considerations that should help guide referral.

BOSTON – An analysis of data from medullary thyroid cancer patients that partitioned the patients into groups with similar overall survival has spurred a rethink of the current American Joint Committee on Cancer (AJCC) staging system.

The results from researchers at Duke University, Durham, N.C., presented at the annual meeting of the Endocrine Society by Dr. Mohamed Abdelgadir Adam, are timely, as the AJCC has embarked on a reconsideration of the staging of cancers, including medullary thyroid cancer (MTC), as part revisions for the eighth edition of the staging system.

“The existing AJCC staging system for MTC appears to be less than optimal in discriminating the risk of mortality among disease stage groups,” said Dr. Adam, who discussed the findings in a video interview.

MTC, a neuroendocrine tumor that affects C cells of the thyroid, comprises 3%-5% of all cases of thyroid cancer and it can be a more aggressive disease than differentiated thyroid cancer. Yet the current AJCC MTC staging system has been extrapolated from differentiated thyroid cancer data.

“We sought to evaluate how well the current AJCC seventh edition stage groupings predict survival for patients with MTC, to suggest a possible staging revision to sharpen estimates of prognosis,” said Dr. Adam.

The researchers utilized the National Cancer Data Base, representing over 70% of incident cancer cases in the United States.

MTC patients who underwent thyroid surgery from 1998 to 2012 were identified. Patients with missing values for pathologic T, N, or M were excluded. The primary outcome in the 3,315 patients was survival.

The researchers used a form of decision-tree analysis called recursive partitioning. In general, recursive partitioning is able to classify a population by splitting subjects into subgroups, each of which is homogeneous based on the particular outcome. In this study, the subgroup allocations were based on T, N, and M stages, with the outcome being overall survival. Kaplan-Meier and adjusted survival analyses enabled survival differences among the four subgroups (groups I, II, III and IV) to be explored.

The four groups were distinct in terms of survival time and allowed more accurate risk stratification. In particular, groups I and II were markedly better distinguished from one another than is the case with the current staging system. Survival differences across the stages were more distinct with the newly created T, N, and M groupings, compared with the current AJCC staging system.

After adjustment, survival differences across TNM groups were more distinct with the newly created TNM groupings (compared to subgroup I, hazard ratio of 3.06 for subgroup II; HR, 6.79 for III; and HR, 17.03 for IV), compared with the current AJCC staging (compared to stage I, HR, 1.45 for stage II; HR, 2.17 for III; and HR, 5.33 for IV).

“The AJCC is reevaluating all staging schemas, including MTC. The current AJCC staging system could be improved with the newly identified TNM groupings suggested here for more accurate patient risk stratification and possibly treatment selection,” said Dr. Adam.

Dr. Adam had no disclosures.

BOSTON – An analysis of data from medullary thyroid cancer patients that partitioned the patients into groups with similar overall survival has spurred a rethink of the current American Joint Committee on Cancer (AJCC) staging system.

The results from researchers at Duke University, Durham, N.C., presented at the annual meeting of the Endocrine Society by Dr. Mohamed Abdelgadir Adam, are timely, as the AJCC has embarked on a reconsideration of the staging of cancers, including medullary thyroid cancer (MTC), as part revisions for the eighth edition of the staging system.

“The existing AJCC staging system for MTC appears to be less than optimal in discriminating the risk of mortality among disease stage groups,” said Dr. Adam, who discussed the findings in a video interview.

MTC, a neuroendocrine tumor that affects C cells of the thyroid, comprises 3%-5% of all cases of thyroid cancer and it can be a more aggressive disease than differentiated thyroid cancer. Yet the current AJCC MTC staging system has been extrapolated from differentiated thyroid cancer data.

“We sought to evaluate how well the current AJCC seventh edition stage groupings predict survival for patients with MTC, to suggest a possible staging revision to sharpen estimates of prognosis,” said Dr. Adam.

The researchers utilized the National Cancer Data Base, representing over 70% of incident cancer cases in the United States.

MTC patients who underwent thyroid surgery from 1998 to 2012 were identified. Patients with missing values for pathologic T, N, or M were excluded. The primary outcome in the 3,315 patients was survival.

The researchers used a form of decision-tree analysis called recursive partitioning. In general, recursive partitioning is able to classify a population by splitting subjects into subgroups, each of which is homogeneous based on the particular outcome. In this study, the subgroup allocations were based on T, N, and M stages, with the outcome being overall survival. Kaplan-Meier and adjusted survival analyses enabled survival differences among the four subgroups (groups I, II, III and IV) to be explored.

The four groups were distinct in terms of survival time and allowed more accurate risk stratification. In particular, groups I and II were markedly better distinguished from one another than is the case with the current staging system. Survival differences across the stages were more distinct with the newly created T, N, and M groupings, compared with the current AJCC staging system.

After adjustment, survival differences across TNM groups were more distinct with the newly created TNM groupings (compared to subgroup I, hazard ratio of 3.06 for subgroup II; HR, 6.79 for III; and HR, 17.03 for IV), compared with the current AJCC staging (compared to stage I, HR, 1.45 for stage II; HR, 2.17 for III; and HR, 5.33 for IV).

“The AJCC is reevaluating all staging schemas, including MTC. The current AJCC staging system could be improved with the newly identified TNM groupings suggested here for more accurate patient risk stratification and possibly treatment selection,” said Dr. Adam.

Dr. Adam had no disclosures.

BOSTON – An analysis of data from medullary thyroid cancer patients that partitioned the patients into groups with similar overall survival has spurred a rethink of the current American Joint Committee on Cancer (AJCC) staging system.

The results from researchers at Duke University, Durham, N.C., presented at the annual meeting of the Endocrine Society by Dr. Mohamed Abdelgadir Adam, are timely, as the AJCC has embarked on a reconsideration of the staging of cancers, including medullary thyroid cancer (MTC), as part revisions for the eighth edition of the staging system.

“The existing AJCC staging system for MTC appears to be less than optimal in discriminating the risk of mortality among disease stage groups,” said Dr. Adam, who discussed the findings in a video interview.

MTC, a neuroendocrine tumor that affects C cells of the thyroid, comprises 3%-5% of all cases of thyroid cancer and it can be a more aggressive disease than differentiated thyroid cancer. Yet the current AJCC MTC staging system has been extrapolated from differentiated thyroid cancer data.

“We sought to evaluate how well the current AJCC seventh edition stage groupings predict survival for patients with MTC, to suggest a possible staging revision to sharpen estimates of prognosis,” said Dr. Adam.

The researchers utilized the National Cancer Data Base, representing over 70% of incident cancer cases in the United States.

MTC patients who underwent thyroid surgery from 1998 to 2012 were identified. Patients with missing values for pathologic T, N, or M were excluded. The primary outcome in the 3,315 patients was survival.

The researchers used a form of decision-tree analysis called recursive partitioning. In general, recursive partitioning is able to classify a population by splitting subjects into subgroups, each of which is homogeneous based on the particular outcome. In this study, the subgroup allocations were based on T, N, and M stages, with the outcome being overall survival. Kaplan-Meier and adjusted survival analyses enabled survival differences among the four subgroups (groups I, II, III and IV) to be explored.

The four groups were distinct in terms of survival time and allowed more accurate risk stratification. In particular, groups I and II were markedly better distinguished from one another than is the case with the current staging system. Survival differences across the stages were more distinct with the newly created T, N, and M groupings, compared with the current AJCC staging system.

After adjustment, survival differences across TNM groups were more distinct with the newly created TNM groupings (compared to subgroup I, hazard ratio of 3.06 for subgroup II; HR, 6.79 for III; and HR, 17.03 for IV), compared with the current AJCC staging (compared to stage I, HR, 1.45 for stage II; HR, 2.17 for III; and HR, 5.33 for IV).

“The AJCC is reevaluating all staging schemas, including MTC. The current AJCC staging system could be improved with the newly identified TNM groupings suggested here for more accurate patient risk stratification and possibly treatment selection,” said Dr. Adam.

Dr. Adam had no disclosures.

Severe sepsis and septic shock syndrome may be rare complications of chikungunya virus infection, according to a recent study in Guadeloupe.

Dr. Bruno Hoen, of the department of infectious diseases, dermatology, and internal medicine at the University Medical Center of Guadeloupe, and his associates studied 110 nonpregnant adults hospitalized at the University Hospital of Pointe-à-Pitre, Guadeloupe, with chikungunya (CHIKV) after a November 2013 outbreak in Guadeloupe. Of all patients who had a positive CHIKV reverse transcription–polymerase chain reaction (RT-PCR) test result, 34 had a common form, 34 had an atypical form, and 42 had a severe form. Among the 42 patients with severe forms, 25 patients had illness consistent with the case definition for severe sepsis and had no other identified cause for this syndrome, and 12 died.

CDC/Cynthia Goldsmith

The 25 patients identified as having severe sepsis had significantly higher occurrences of cardiac, respiratory, and renal manifestations upon admission to hospital. They also had significantly higher leukocyte counts and levels of serum lactate dehydrogenase, aspartate aminotransferase, and creatinine – all clinical and laboratory indicators of sepsis – than patients without severe sepsis or septic shock. In addition, the mortality rate for the patients with severe sepsis was significantly higher than that in patients without severe sepsis or septic shock (48% vs. 3%; P less than .001).

As none of the 25 patients with severe sepsis or septic shock in the early stages of CHIKV had another organism that could be identified as a potential cause of sepsis, the researchers concluded that this finding strongly suggests that CHIKV can, in rare cases, cause severe sepsis and septic shock syndromes, an observation that had not been reported until very recently.

Dr. Hoen and his colleagues said additional studies are needed to identify any background characteristics that might be associated with the onset of severe sepsis or septic shock. The authors reported no conflicts of interest.

Read the full study in Emerging Infectious Diseases (2016 May. doi: 10.3201/eid2205.151449).

llaubach@frontlinemedcom.com

Severe sepsis and septic shock syndrome may be rare complications of chikungunya virus infection, according to a recent study in Guadeloupe.

Dr. Bruno Hoen, of the department of infectious diseases, dermatology, and internal medicine at the University Medical Center of Guadeloupe, and his associates studied 110 nonpregnant adults hospitalized at the University Hospital of Pointe-à-Pitre, Guadeloupe, with chikungunya (CHIKV) after a November 2013 outbreak in Guadeloupe. Of all patients who had a positive CHIKV reverse transcription–polymerase chain reaction (RT-PCR) test result, 34 had a common form, 34 had an atypical form, and 42 had a severe form. Among the 42 patients with severe forms, 25 patients had illness consistent with the case definition for severe sepsis and had no other identified cause for this syndrome, and 12 died.

CDC/Cynthia Goldsmith

The 25 patients identified as having severe sepsis had significantly higher occurrences of cardiac, respiratory, and renal manifestations upon admission to hospital. They also had significantly higher leukocyte counts and levels of serum lactate dehydrogenase, aspartate aminotransferase, and creatinine – all clinical and laboratory indicators of sepsis – than patients without severe sepsis or septic shock. In addition, the mortality rate for the patients with severe sepsis was significantly higher than that in patients without severe sepsis or septic shock (48% vs. 3%; P less than .001).

As none of the 25 patients with severe sepsis or septic shock in the early stages of CHIKV had another organism that could be identified as a potential cause of sepsis, the researchers concluded that this finding strongly suggests that CHIKV can, in rare cases, cause severe sepsis and septic shock syndromes, an observation that had not been reported until very recently.

Dr. Hoen and his colleagues said additional studies are needed to identify any background characteristics that might be associated with the onset of severe sepsis or septic shock. The authors reported no conflicts of interest.

Read the full study in Emerging Infectious Diseases (2016 May. doi: 10.3201/eid2205.151449).

llaubach@frontlinemedcom.com

Severe sepsis and septic shock syndrome may be rare complications of chikungunya virus infection, according to a recent study in Guadeloupe.

Dr. Bruno Hoen, of the department of infectious diseases, dermatology, and internal medicine at the University Medical Center of Guadeloupe, and his associates studied 110 nonpregnant adults hospitalized at the University Hospital of Pointe-à-Pitre, Guadeloupe, with chikungunya (CHIKV) after a November 2013 outbreak in Guadeloupe. Of all patients who had a positive CHIKV reverse transcription–polymerase chain reaction (RT-PCR) test result, 34 had a common form, 34 had an atypical form, and 42 had a severe form. Among the 42 patients with severe forms, 25 patients had illness consistent with the case definition for severe sepsis and had no other identified cause for this syndrome, and 12 died.

CDC/Cynthia Goldsmith

The 25 patients identified as having severe sepsis had significantly higher occurrences of cardiac, respiratory, and renal manifestations upon admission to hospital. They also had significantly higher leukocyte counts and levels of serum lactate dehydrogenase, aspartate aminotransferase, and creatinine – all clinical and laboratory indicators of sepsis – than patients without severe sepsis or septic shock. In addition, the mortality rate for the patients with severe sepsis was significantly higher than that in patients without severe sepsis or septic shock (48% vs. 3%; P less than .001).

As none of the 25 patients with severe sepsis or septic shock in the early stages of CHIKV had another organism that could be identified as a potential cause of sepsis, the researchers concluded that this finding strongly suggests that CHIKV can, in rare cases, cause severe sepsis and septic shock syndromes, an observation that had not been reported until very recently.

Dr. Hoen and his colleagues said additional studies are needed to identify any background characteristics that might be associated with the onset of severe sepsis or septic shock. The authors reported no conflicts of interest.

Read the full study in Emerging Infectious Diseases (2016 May. doi: 10.3201/eid2205.151449).

llaubach@frontlinemedcom.com

CHICAGO – Ischemic postconditioning in patients with ST-segment elevation myocardial infarction failed to significantly reduce death from any cause or hospitalization for heart failure in the randomized, controlled DANAMI 3-iPOST trial.

At a mean follow-up of 37.5 months, the primary composite endpoint of death from any cause and hospitalization for heart failure occurred in 69 of 617 patients with STEMI who received standard angioplasty and in 65 of 617 patients who received ischemic postconditioning in DANAMI 3-iPOST (the Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: iPOST conditioning during primary PCI). The 7% difference (hazard ratio, 0.93) was not statistically significant, Dr. Thomas Engstrøm reported at the annual meeting of the American College of Cardiology.

Sharon Worcester/Frontline Medical News

For the individual component of all-cause mortality, the reduction in the ischemic postconditioning group was 25%, occurring in 50 patients, compared with 38 in the conventionally treated group (hazard ratio, 0.75), but this difference also did not reach statistical significance, Dr. Engstrøm said.

Thirty patients in each group required hospitalization for heart failure.

However, an improvement in a secondary endpoint of left ventricular ejection fraction above 45% in patients with anterior infarcts was statistically significant, occurring in 72% of patients in the standard angioplasty group and 80% of those in the ischemic postconditioning group, said Dr. Engstrøm of Rigshospitalet University of Copenhagen.

This finding may translate into improved survival with longer follow-up, he noted.

Patients in the DANAMI-3 iPOST trial, who had a mean age of age 61 years, had acute STEMI (ST-segment elevation MI) symptoms of less than 12 hours’ duration at the time of randomization. They were followed for at least 2 years.

Ischemic postconditioning – a variation on angioplasty that involves using 30-second bursts of blood flow interspersed with 30-second pauses to restore blood flow to the heart – was shown in earlier studies to improve ST-segment resolution, reduce damage to heart muscle, and – in some patients – limit the extent of reperfusion injury.

Whether these factors would reduce hospitalizations or improve patient survival remained unclear, Dr. Engstrøm said.

Abrupt reperfusion by angioplasty may itself damage the heart muscle. In fact, up to 35% of patients may experience such injury during angioplasty.

“The thinking was that performing the reperfusion in a gentle, graded fashion would protect the heart against reperfusion injury,” Dr. Engstrøm explained.

The findings of DANAMI 3-iPOST – the first large clinical trial designed to evaluate clinical outcomes in STEMI patients (as opposed to surrogate endpoints such as ST-segment resolution) were disappointing, but larger trials may be required to definitively establish whether ischemic postconditioning improves clinical outcomes, Dr. Engstrøm said.

The DANAMI 3-iPOST trial was funded by the Danish Agency for Science, Technology, and Innovation and the Danish Council for Strategic Research. Dr. Engstrøm reported having no relevant financial disclosures.

sworcester@frontlinemedcom.com

CHICAGO – Ischemic postconditioning in patients with ST-segment elevation myocardial infarction failed to significantly reduce death from any cause or hospitalization for heart failure in the randomized, controlled DANAMI 3-iPOST trial.

At a mean follow-up of 37.5 months, the primary composite endpoint of death from any cause and hospitalization for heart failure occurred in 69 of 617 patients with STEMI who received standard angioplasty and in 65 of 617 patients who received ischemic postconditioning in DANAMI 3-iPOST (the Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: iPOST conditioning during primary PCI). The 7% difference (hazard ratio, 0.93) was not statistically significant, Dr. Thomas Engstrøm reported at the annual meeting of the American College of Cardiology.

Sharon Worcester/Frontline Medical News

For the individual component of all-cause mortality, the reduction in the ischemic postconditioning group was 25%, occurring in 50 patients, compared with 38 in the conventionally treated group (hazard ratio, 0.75), but this difference also did not reach statistical significance, Dr. Engstrøm said.

Thirty patients in each group required hospitalization for heart failure.

However, an improvement in a secondary endpoint of left ventricular ejection fraction above 45% in patients with anterior infarcts was statistically significant, occurring in 72% of patients in the standard angioplasty group and 80% of those in the ischemic postconditioning group, said Dr. Engstrøm of Rigshospitalet University of Copenhagen.

This finding may translate into improved survival with longer follow-up, he noted.

Patients in the DANAMI-3 iPOST trial, who had a mean age of age 61 years, had acute STEMI (ST-segment elevation MI) symptoms of less than 12 hours’ duration at the time of randomization. They were followed for at least 2 years.

Ischemic postconditioning – a variation on angioplasty that involves using 30-second bursts of blood flow interspersed with 30-second pauses to restore blood flow to the heart – was shown in earlier studies to improve ST-segment resolution, reduce damage to heart muscle, and – in some patients – limit the extent of reperfusion injury.

Whether these factors would reduce hospitalizations or improve patient survival remained unclear, Dr. Engstrøm said.

Abrupt reperfusion by angioplasty may itself damage the heart muscle. In fact, up to 35% of patients may experience such injury during angioplasty.

“The thinking was that performing the reperfusion in a gentle, graded fashion would protect the heart against reperfusion injury,” Dr. Engstrøm explained.

The findings of DANAMI 3-iPOST – the first large clinical trial designed to evaluate clinical outcomes in STEMI patients (as opposed to surrogate endpoints such as ST-segment resolution) were disappointing, but larger trials may be required to definitively establish whether ischemic postconditioning improves clinical outcomes, Dr. Engstrøm said.

The DANAMI 3-iPOST trial was funded by the Danish Agency for Science, Technology, and Innovation and the Danish Council for Strategic Research. Dr. Engstrøm reported having no relevant financial disclosures.

sworcester@frontlinemedcom.com

CHICAGO – Ischemic postconditioning in patients with ST-segment elevation myocardial infarction failed to significantly reduce death from any cause or hospitalization for heart failure in the randomized, controlled DANAMI 3-iPOST trial.

At a mean follow-up of 37.5 months, the primary composite endpoint of death from any cause and hospitalization for heart failure occurred in 69 of 617 patients with STEMI who received standard angioplasty and in 65 of 617 patients who received ischemic postconditioning in DANAMI 3-iPOST (the Third Danish Study of Optimal Acute Treatment of Patients With ST-Segment Elevation Myocardial Infarction: iPOST conditioning during primary PCI). The 7% difference (hazard ratio, 0.93) was not statistically significant, Dr. Thomas Engstrøm reported at the annual meeting of the American College of Cardiology.

Sharon Worcester/Frontline Medical News

For the individual component of all-cause mortality, the reduction in the ischemic postconditioning group was 25%, occurring in 50 patients, compared with 38 in the conventionally treated group (hazard ratio, 0.75), but this difference also did not reach statistical significance, Dr. Engstrøm said.

Thirty patients in each group required hospitalization for heart failure.

However, an improvement in a secondary endpoint of left ventricular ejection fraction above 45% in patients with anterior infarcts was statistically significant, occurring in 72% of patients in the standard angioplasty group and 80% of those in the ischemic postconditioning group, said Dr. Engstrøm of Rigshospitalet University of Copenhagen.

This finding may translate into improved survival with longer follow-up, he noted.

Patients in the DANAMI-3 iPOST trial, who had a mean age of age 61 years, had acute STEMI (ST-segment elevation MI) symptoms of less than 12 hours’ duration at the time of randomization. They were followed for at least 2 years.

Ischemic postconditioning – a variation on angioplasty that involves using 30-second bursts of blood flow interspersed with 30-second pauses to restore blood flow to the heart – was shown in earlier studies to improve ST-segment resolution, reduce damage to heart muscle, and – in some patients – limit the extent of reperfusion injury.

Whether these factors would reduce hospitalizations or improve patient survival remained unclear, Dr. Engstrøm said.

Abrupt reperfusion by angioplasty may itself damage the heart muscle. In fact, up to 35% of patients may experience such injury during angioplasty.

“The thinking was that performing the reperfusion in a gentle, graded fashion would protect the heart against reperfusion injury,” Dr. Engstrøm explained.

The findings of DANAMI 3-iPOST – the first large clinical trial designed to evaluate clinical outcomes in STEMI patients (as opposed to surrogate endpoints such as ST-segment resolution) were disappointing, but larger trials may be required to definitively establish whether ischemic postconditioning improves clinical outcomes, Dr. Engstrøm said.

The DANAMI 3-iPOST trial was funded by the Danish Agency for Science, Technology, and Innovation and the Danish Council for Strategic Research. Dr. Engstrøm reported having no relevant financial disclosures.

sworcester@frontlinemedcom.com

CHICAGO – Results from the HOPE-3 trial confirm what guidelines have already recommended: patients with intermediate risk for cardiovascular disease should be treated for primary prevention of coronary event, Dr. Prakash Deedwania said in an interview at the annual meeting of the American College of Cardiology.

In the Heart Outcomes Prevention Evaluation (HOPE)-3 trial, nearly 13,000 intermediate-risk men and women with no baseline cardiovascular disease were randomized to either lipid lowering with rosuvastatin at 10 mg/day or placebo, dual-antihypertensive therapy with candesartan plus chlorothiazide or placebo regardless of baseline blood pressure, or all three drugs or placebo. After a median of 5.6 years, the combined-therapy group had a 29% reduction in the composite of cardiovascular death or nonfatal MI or stroke, compared with placebo-treated controls, regardless of baseline LDL-cholesterol level. However, only subjects with a baseline pressure of greater than 143.5 mm Hg benefited from the dual-antihypertensive therapy.

In a video interview, Dr. Deedwania, professor of medicine at the University of California, San Francisco, Fresno, gave three takeaways from the HOPE-3 trial regarding primary prevention of cardiovascular events in patients at intermediate risk, how the results of the dual-antihypertensive treatment arm match up to guidelines, and whether there’s a future for the polypill.

Dr. Deedwania has received consultant fees and/or honoraria from Amgen, Pfizer, and Sanofi.

chackett@frontlinemedcom.com

CHICAGO – Results from the HOPE-3 trial confirm what guidelines have already recommended: patients with intermediate risk for cardiovascular disease should be treated for primary prevention of coronary event, Dr. Prakash Deedwania said in an interview at the annual meeting of the American College of Cardiology.

In the Heart Outcomes Prevention Evaluation (HOPE)-3 trial, nearly 13,000 intermediate-risk men and women with no baseline cardiovascular disease were randomized to either lipid lowering with rosuvastatin at 10 mg/day or placebo, dual-antihypertensive therapy with candesartan plus chlorothiazide or placebo regardless of baseline blood pressure, or all three drugs or placebo. After a median of 5.6 years, the combined-therapy group had a 29% reduction in the composite of cardiovascular death or nonfatal MI or stroke, compared with placebo-treated controls, regardless of baseline LDL-cholesterol level. However, only subjects with a baseline pressure of greater than 143.5 mm Hg benefited from the dual-antihypertensive therapy.

In a video interview, Dr. Deedwania, professor of medicine at the University of California, San Francisco, Fresno, gave three takeaways from the HOPE-3 trial regarding primary prevention of cardiovascular events in patients at intermediate risk, how the results of the dual-antihypertensive treatment arm match up to guidelines, and whether there’s a future for the polypill.

Dr. Deedwania has received consultant fees and/or honoraria from Amgen, Pfizer, and Sanofi.

chackett@frontlinemedcom.com

CHICAGO – Results from the HOPE-3 trial confirm what guidelines have already recommended: patients with intermediate risk for cardiovascular disease should be treated for primary prevention of coronary event, Dr. Prakash Deedwania said in an interview at the annual meeting of the American College of Cardiology.

In the Heart Outcomes Prevention Evaluation (HOPE)-3 trial, nearly 13,000 intermediate-risk men and women with no baseline cardiovascular disease were randomized to either lipid lowering with rosuvastatin at 10 mg/day or placebo, dual-antihypertensive therapy with candesartan plus chlorothiazide or placebo regardless of baseline blood pressure, or all three drugs or placebo. After a median of 5.6 years, the combined-therapy group had a 29% reduction in the composite of cardiovascular death or nonfatal MI or stroke, compared with placebo-treated controls, regardless of baseline LDL-cholesterol level. However, only subjects with a baseline pressure of greater than 143.5 mm Hg benefited from the dual-antihypertensive therapy.

In a video interview, Dr. Deedwania, professor of medicine at the University of California, San Francisco, Fresno, gave three takeaways from the HOPE-3 trial regarding primary prevention of cardiovascular events in patients at intermediate risk, how the results of the dual-antihypertensive treatment arm match up to guidelines, and whether there’s a future for the polypill.

Dr. Deedwania has received consultant fees and/or honoraria from Amgen, Pfizer, and Sanofi.

chackett@frontlinemedcom.com

AMSTERDAM – Accounting for less than 1% of cases, Propionibacterium acnes has been considered an uncommon cause of infective endocarditis.

But data presented at the annual congress of the European Society of Clinical Microbiology and Infectious Diseases suggest that the common anaerobe may be responsible for many more cases than is now believed. The bacteria are difficult to culture and grow very slowly, Dr. Jona Banzon said at the meeting. Incubating it for the standard 5 days may simply not be long enough.

“Due to this slow-growing nature, the standard incubation period may not be enough to detect it,” said Dr. Banzon, an infectious disease fellow at the Cleveland Clinic. “And since P. acnes is part of our commensal flora, it’s frequently a contaminate in culture, and we might be inappropriately dismissing it as such. In fact, we now wonder if this lack of extended incubation may be accounting for a significant proportion of negative blood cultures, and whether more prosthetic valve endocarditis than we think is actually being caused by P. acnes.”

Dr. Banzon presented a series of 23 cases included in the Cleveland Clinic Infective Endocarditis Registry from the period of 2007-2015. All had P. acnes confirmed as the causative organism. The group comprises 3.3% of the institution’s entire infective endocarditis registry, “making infective carditis with P. acnes already much more common than it is said to be in the literature,” she noted.

All of the cases were confirmed by any of the following standards:

• Two or more blood cultures positive for P. acnes.

• Two or more valve cultures positive for P. acnes.

• Two or more valve sequencing rests positive for P. acnes.

• At least two of the following: a positive blood culture, a positive valve culture or valve sequencing, or histopathologic demonstration of microorganism consistent with P. acnes.

Of the cohort, 22 had prosthetic valve endocarditis. One patient had endocarditis on a native valve. This is an important point, Dr. Banzon said.

The organism is being increasingly recognized for causing infections of prosthetic material, including shoulder joint infections and shunts, but it rarely seems to affect native tissue. The patient who had native valve endocarditis had experienced an episode of Staphylococcus aureus endocarditis about 18 months earlier. He was not treated surgically, and ended up with a damaged valve. After the initial illness, he was readmitted several times with symptoms of endocarditis, but all of his blood cultures were negative. This was attributed to the receipt of antibiotics. “When he was finally operated on, there were three valve sequencing specimens and all were positive for P. acnes,” Dr. Banzon said.

The patients in the cohort were a mean of 74 years old; about 75% were men. All of the cases were left-sided endocarditis, with the majority (74%) involving the aortic valve. Other sites included the mitral valve (18%), aortic plus mitral (4%), and aortic plus tricuspid (4%).

The most common predisposing factor was having a prosthetic valve (96%). Other factors included having a cardiac implantable device (17%), and a prior episode of infective endocarditis (13%). None of the patients had indwelling vascular catheters or used injectable drugs.

The cases presented with severe disease, Dr. Banzon said. Almost half (48%) had a perivalvular abscess at presentation. A third (35%) had valve dehiscence, and 35% had severe valvular regurgitation. There was a vegetation of more than 1 cm in 9% of cases.

Emboli were not uncommon; 17% had emboli in the central nervous system, and 17% had peripheral emboli. Two of these patients had kidney and spleen infarcts and two had acute arterial thromboembolism that required thrombectomy.

All of the patients underwent blood cultures; overall, 30% of the cultures were positive for P. acnes. But there were “striking differences” when the tests were broken down by incubation time, Dr. Banzon said.

Most of the cultures (16) were incubated for the standard of 5 days or less. Among these, 12.5% were positive. However, cultures on seven patients were incubated for more than 5 days and in this group, 71.4% were positive for P. acnes. The median time to positivity overall was 7 days, with a range of 3-9 days.

Other diagnostic methods were important in closing this gap, she said. Valve culturing was positive in 57% of the cases, while valve sequencing was positive in 95%. The median time to positive for valve culture was somewhat shorter than for blood culture (5.5 days).

In nine cases, no organism would have been identified without valve sequencing, Dr. Banzon said.

Because they presented with severe disease, almost all of the patients (22) underwent surgery as their intimal treatment. At the time of surgery, everyone was taking an antibiotic that covered P. acnes. Single-agent therapy was the definitive treatment for most, with vancomycin being most commonly employed (59%), followed by ceftriaxone (25%). A few patients had a combination of both drugs or a combination of vancomycin and rifampin. One patient took penicillin.

The single patient who was medically treated received 6 weeks of intravenous ceftriaxone. After 1 month, he was readmitted with blood cultures positive for P. acnes. He underwent surgery and a valve sequencing confirmed P. acnes as the infective agent.

There were two in-hospital deaths, but the rest of the patients were discharged on antibiotic therapy and recovered with no additional deaths or relapses.

The extended time P. acnes required to show in culture was enough for the Cleveland Clinic to reconsider incubation guidelines for the microorganism, Dr. Banzon said.

“There are enough cases taking 9 or 10 days that we now always hold these cultures for at least 10 days when we’re looking for P. acnes.”

She had no financial disclosures.

msullivan@frontlinemedcom.com

AMSTERDAM – Accounting for less than 1% of cases, Propionibacterium acnes has been considered an uncommon cause of infective endocarditis.

But data presented at the annual congress of the European Society of Clinical Microbiology and Infectious Diseases suggest that the common anaerobe may be responsible for many more cases than is now believed. The bacteria are difficult to culture and grow very slowly, Dr. Jona Banzon said at the meeting. Incubating it for the standard 5 days may simply not be long enough.

“Due to this slow-growing nature, the standard incubation period may not be enough to detect it,” said Dr. Banzon, an infectious disease fellow at the Cleveland Clinic. “And since P. acnes is part of our commensal flora, it’s frequently a contaminate in culture, and we might be inappropriately dismissing it as such. In fact, we now wonder if this lack of extended incubation may be accounting for a significant proportion of negative blood cultures, and whether more prosthetic valve endocarditis than we think is actually being caused by P. acnes.”

Dr. Banzon presented a series of 23 cases included in the Cleveland Clinic Infective Endocarditis Registry from the period of 2007-2015. All had P. acnes confirmed as the causative organism. The group comprises 3.3% of the institution’s entire infective endocarditis registry, “making infective carditis with P. acnes already much more common than it is said to be in the literature,” she noted.

All of the cases were confirmed by any of the following standards:

• Two or more blood cultures positive for P. acnes.

• Two or more valve cultures positive for P. acnes.

• Two or more valve sequencing rests positive for P. acnes.

• At least two of the following: a positive blood culture, a positive valve culture or valve sequencing, or histopathologic demonstration of microorganism consistent with P. acnes.

Of the cohort, 22 had prosthetic valve endocarditis. One patient had endocarditis on a native valve. This is an important point, Dr. Banzon said.

The organism is being increasingly recognized for causing infections of prosthetic material, including shoulder joint infections and shunts, but it rarely seems to affect native tissue. The patient who had native valve endocarditis had experienced an episode of Staphylococcus aureus endocarditis about 18 months earlier. He was not treated surgically, and ended up with a damaged valve. After the initial illness, he was readmitted several times with symptoms of endocarditis, but all of his blood cultures were negative. This was attributed to the receipt of antibiotics. “When he was finally operated on, there were three valve sequencing specimens and all were positive for P. acnes,” Dr. Banzon said.

The patients in the cohort were a mean of 74 years old; about 75% were men. All of the cases were left-sided endocarditis, with the majority (74%) involving the aortic valve. Other sites included the mitral valve (18%), aortic plus mitral (4%), and aortic plus tricuspid (4%).

The most common predisposing factor was having a prosthetic valve (96%). Other factors included having a cardiac implantable device (17%), and a prior episode of infective endocarditis (13%). None of the patients had indwelling vascular catheters or used injectable drugs.

The cases presented with severe disease, Dr. Banzon said. Almost half (48%) had a perivalvular abscess at presentation. A third (35%) had valve dehiscence, and 35% had severe valvular regurgitation. There was a vegetation of more than 1 cm in 9% of cases.

Emboli were not uncommon; 17% had emboli in the central nervous system, and 17% had peripheral emboli. Two of these patients had kidney and spleen infarcts and two had acute arterial thromboembolism that required thrombectomy.

All of the patients underwent blood cultures; overall, 30% of the cultures were positive for P. acnes. But there were “striking differences” when the tests were broken down by incubation time, Dr. Banzon said.

Most of the cultures (16) were incubated for the standard of 5 days or less. Among these, 12.5% were positive. However, cultures on seven patients were incubated for more than 5 days and in this group, 71.4% were positive for P. acnes. The median time to positivity overall was 7 days, with a range of 3-9 days.

Other diagnostic methods were important in closing this gap, she said. Valve culturing was positive in 57% of the cases, while valve sequencing was positive in 95%. The median time to positive for valve culture was somewhat shorter than for blood culture (5.5 days).

In nine cases, no organism would have been identified without valve sequencing, Dr. Banzon said.

Because they presented with severe disease, almost all of the patients (22) underwent surgery as their intimal treatment. At the time of surgery, everyone was taking an antibiotic that covered P. acnes. Single-agent therapy was the definitive treatment for most, with vancomycin being most commonly employed (59%), followed by ceftriaxone (25%). A few patients had a combination of both drugs or a combination of vancomycin and rifampin. One patient took penicillin.

The single patient who was medically treated received 6 weeks of intravenous ceftriaxone. After 1 month, he was readmitted with blood cultures positive for P. acnes. He underwent surgery and a valve sequencing confirmed P. acnes as the infective agent.

There were two in-hospital deaths, but the rest of the patients were discharged on antibiotic therapy and recovered with no additional deaths or relapses.

The extended time P. acnes required to show in culture was enough for the Cleveland Clinic to reconsider incubation guidelines for the microorganism, Dr. Banzon said.

“There are enough cases taking 9 or 10 days that we now always hold these cultures for at least 10 days when we’re looking for P. acnes.”

She had no financial disclosures.

msullivan@frontlinemedcom.com

AMSTERDAM – Accounting for less than 1% of cases, Propionibacterium acnes has been considered an uncommon cause of infective endocarditis.

But data presented at the annual congress of the European Society of Clinical Microbiology and Infectious Diseases suggest that the common anaerobe may be responsible for many more cases than is now believed. The bacteria are difficult to culture and grow very slowly, Dr. Jona Banzon said at the meeting. Incubating it for the standard 5 days may simply not be long enough.

“Due to this slow-growing nature, the standard incubation period may not be enough to detect it,” said Dr. Banzon, an infectious disease fellow at the Cleveland Clinic. “And since P. acnes is part of our commensal flora, it’s frequently a contaminate in culture, and we might be inappropriately dismissing it as such. In fact, we now wonder if this lack of extended incubation may be accounting for a significant proportion of negative blood cultures, and whether more prosthetic valve endocarditis than we think is actually being caused by P. acnes.”

Dr. Banzon presented a series of 23 cases included in the Cleveland Clinic Infective Endocarditis Registry from the period of 2007-2015. All had P. acnes confirmed as the causative organism. The group comprises 3.3% of the institution’s entire infective endocarditis registry, “making infective carditis with P. acnes already much more common than it is said to be in the literature,” she noted.

All of the cases were confirmed by any of the following standards:

• Two or more blood cultures positive for P. acnes.

• Two or more valve cultures positive for P. acnes.

• Two or more valve sequencing rests positive for P. acnes.

• At least two of the following: a positive blood culture, a positive valve culture or valve sequencing, or histopathologic demonstration of microorganism consistent with P. acnes.

Of the cohort, 22 had prosthetic valve endocarditis. One patient had endocarditis on a native valve. This is an important point, Dr. Banzon said.

The organism is being increasingly recognized for causing infections of prosthetic material, including shoulder joint infections and shunts, but it rarely seems to affect native tissue. The patient who had native valve endocarditis had experienced an episode of Staphylococcus aureus endocarditis about 18 months earlier. He was not treated surgically, and ended up with a damaged valve. After the initial illness, he was readmitted several times with symptoms of endocarditis, but all of his blood cultures were negative. This was attributed to the receipt of antibiotics. “When he was finally operated on, there were three valve sequencing specimens and all were positive for P. acnes,” Dr. Banzon said.

The patients in the cohort were a mean of 74 years old; about 75% were men. All of the cases were left-sided endocarditis, with the majority (74%) involving the aortic valve. Other sites included the mitral valve (18%), aortic plus mitral (4%), and aortic plus tricuspid (4%).

The most common predisposing factor was having a prosthetic valve (96%). Other factors included having a cardiac implantable device (17%), and a prior episode of infective endocarditis (13%). None of the patients had indwelling vascular catheters or used injectable drugs.

The cases presented with severe disease, Dr. Banzon said. Almost half (48%) had a perivalvular abscess at presentation. A third (35%) had valve dehiscence, and 35% had severe valvular regurgitation. There was a vegetation of more than 1 cm in 9% of cases.

Emboli were not uncommon; 17% had emboli in the central nervous system, and 17% had peripheral emboli. Two of these patients had kidney and spleen infarcts and two had acute arterial thromboembolism that required thrombectomy.

All of the patients underwent blood cultures; overall, 30% of the cultures were positive for P. acnes. But there were “striking differences” when the tests were broken down by incubation time, Dr. Banzon said.

Most of the cultures (16) were incubated for the standard of 5 days or less. Among these, 12.5% were positive. However, cultures on seven patients were incubated for more than 5 days and in this group, 71.4% were positive for P. acnes. The median time to positivity overall was 7 days, with a range of 3-9 days.

Other diagnostic methods were important in closing this gap, she said. Valve culturing was positive in 57% of the cases, while valve sequencing was positive in 95%. The median time to positive for valve culture was somewhat shorter than for blood culture (5.5 days).

In nine cases, no organism would have been identified without valve sequencing, Dr. Banzon said.

Because they presented with severe disease, almost all of the patients (22) underwent surgery as their intimal treatment. At the time of surgery, everyone was taking an antibiotic that covered P. acnes. Single-agent therapy was the definitive treatment for most, with vancomycin being most commonly employed (59%), followed by ceftriaxone (25%). A few patients had a combination of both drugs or a combination of vancomycin and rifampin. One patient took penicillin.

The single patient who was medically treated received 6 weeks of intravenous ceftriaxone. After 1 month, he was readmitted with blood cultures positive for P. acnes. He underwent surgery and a valve sequencing confirmed P. acnes as the infective agent.

There were two in-hospital deaths, but the rest of the patients were discharged on antibiotic therapy and recovered with no additional deaths or relapses.

The extended time P. acnes required to show in culture was enough for the Cleveland Clinic to reconsider incubation guidelines for the microorganism, Dr. Banzon said.

“There are enough cases taking 9 or 10 days that we now always hold these cultures for at least 10 days when we’re looking for P. acnes.”

She had no financial disclosures.

msullivan@frontlinemedcom.com

Atopy was not related to development of eczema or asthma in children under age 13 years, according to Ann-Marie Malby Schoos, Ph.D., and her associates at the University of Copenhagen.

Allergic sensitization increased with age in the 399 children tested, rising from 12% at 6 months to 54% at 13 years. The incidence of asthma was highest at age 4 years at 16%, but decreased afterward, falling to 12% at 13 years. The incidence of eczema peaked at 39% in children aged 1.5 years old, but decreased steadily to only 12% in 13-year-olds.

©marekuliasz/Thinkstock

Asthma and allergic sensitization were related only in late childhood, with an odds ratio of 4.49 in 13-year-olds. This pattern was seen throughout allergic sensitization subgroups. There were strong associations between eczema and allergic sensitization at 6 months (OR, 6.02), 1.5 years (OR, 2.06), and 6 years (OR, 2.77), but no association at 13 years. The proportion of children with allergic sensitization who did not have asthma or eczema also increased with age.

“The tradition of using atopy as a particular endotype of asthma and eczema seems unfounded because it depends on the method of testing for sensitization, type of allergens, and age of the patient. This questions the relevance of the terms atopic asthma and atopic eczema as true endotypes,” the investigators concluded.

Find the full study in the Journal of Allergy and Clinical Immunology (doi: 10.1016/j.jaci.2015.10.004).

lfranki@frontlinemedcom.com

Atopy was not related to development of eczema or asthma in children under age 13 years, according to Ann-Marie Malby Schoos, Ph.D., and her associates at the University of Copenhagen.

Allergic sensitization increased with age in the 399 children tested, rising from 12% at 6 months to 54% at 13 years. The incidence of asthma was highest at age 4 years at 16%, but decreased afterward, falling to 12% at 13 years. The incidence of eczema peaked at 39% in children aged 1.5 years old, but decreased steadily to only 12% in 13-year-olds.

©marekuliasz/Thinkstock

Asthma and allergic sensitization were related only in late childhood, with an odds ratio of 4.49 in 13-year-olds. This pattern was seen throughout allergic sensitization subgroups. There were strong associations between eczema and allergic sensitization at 6 months (OR, 6.02), 1.5 years (OR, 2.06), and 6 years (OR, 2.77), but no association at 13 years. The proportion of children with allergic sensitization who did not have asthma or eczema also increased with age.

“The tradition of using atopy as a particular endotype of asthma and eczema seems unfounded because it depends on the method of testing for sensitization, type of allergens, and age of the patient. This questions the relevance of the terms atopic asthma and atopic eczema as true endotypes,” the investigators concluded.

Find the full study in the Journal of Allergy and Clinical Immunology (doi: 10.1016/j.jaci.2015.10.004).

lfranki@frontlinemedcom.com

Atopy was not related to development of eczema or asthma in children under age 13 years, according to Ann-Marie Malby Schoos, Ph.D., and her associates at the University of Copenhagen.

Allergic sensitization increased with age in the 399 children tested, rising from 12% at 6 months to 54% at 13 years. The incidence of asthma was highest at age 4 years at 16%, but decreased afterward, falling to 12% at 13 years. The incidence of eczema peaked at 39% in children aged 1.5 years old, but decreased steadily to only 12% in 13-year-olds.

©marekuliasz/Thinkstock

Asthma and allergic sensitization were related only in late childhood, with an odds ratio of 4.49 in 13-year-olds. This pattern was seen throughout allergic sensitization subgroups. There were strong associations between eczema and allergic sensitization at 6 months (OR, 6.02), 1.5 years (OR, 2.06), and 6 years (OR, 2.77), but no association at 13 years. The proportion of children with allergic sensitization who did not have asthma or eczema also increased with age.

“The tradition of using atopy as a particular endotype of asthma and eczema seems unfounded because it depends on the method of testing for sensitization, type of allergens, and age of the patient. This questions the relevance of the terms atopic asthma and atopic eczema as true endotypes,” the investigators concluded.

Find the full study in the Journal of Allergy and Clinical Immunology (doi: 10.1016/j.jaci.2015.10.004).

lfranki@frontlinemedcom.com