In the last 30 years, there have been immense advances in the treatment and prevention of sudden cardiac arrest, including beta-blocker therapy and automatic implantable cardiac defibrillators.

In addition, communities have organized emergency medical systems (EMS) designed to provide early cardiac care for the prevention and treatment of cardiac arrest occurring outside the hospital (OHCA). One of the great frustrations of physicians working in the EMS environment is the successful cardiac resuscitation for the patient who is left with severe neurological impairment or brain death. It is clear that resuscitation of the brain is very time dependent. Complete interruption of blood flow to the brain leads to the loss of consciousness within seconds and death of vulnerable neurons in several brain regions occurs within minutes, whereas 20-40 minutes of ischemia is required to kill cardiac myocytes.

To improve survival and prevent the neurological sequelae of OHCA, total body hypothermia is advised based on animal laboratory experiments and a few small clinical studies carried out in a total of 179 OHCA patients (N. Engl. J. Med. 2002;346:557-63 and 549-56).

Both studies show both a neurological and survival benefit – particularly in patients resuscitated from ventricular fibrillation – in comatose patients in whom resuscitation was achieved within 5-10 minutes after witnessed cardiac arrest when cooled to 32-34 degrees Celsius within 60 minutes of collapse. These studies led to the recommendation by the International Liaison Committee on Resuscitation (Circulation 2004;110;3385-97) that cooling to 32-34 degrees Celsius for 12-24 hours should be used in unconscious patients with OHCA with VF and possibly non-VF arrests.

These recommendations were supported by the AHA Guideline Committee (Circulation 2010;122:S768-86) As a result, cooling comatose OHCA patients after resuscitation is widely used in emergency departments in the United States and Europe with the use of a variety of devices and techniques including large volume saline, external cooling devices, intravenous catheter devices, and intranasal devices. When hypothermia was initially recommended, a number of questions were unanswered and remain unanswered despite multiple publications and wide clinical experience in the succeeding 12 years. Some of those questions include the timing, duration, and intensity of cooling, the preferable technique of cooling, and risk and benefits of the different cooling techniques.

In the United States, pressure infusion of 2 liters of ice cold saline is the usual initial method of cooling to 32-34 degrees Celsius followed by 12-36 hours with surface cooling.

Investigators in Seattle randomized OHCA patients prior to hypothermia or standard therapy with both VF and non-VF rhythms before hospitalization to improve the previous reported benefit when initiated in hospital (JAMA 2014;311;45-52).

The initiation of prehospital therapy achieved cooling 1 hour earlier than in previous hospitalization studies. The result in 1,359 OHCAs over a 5-year period raises important questions about the benefit of hypothermia. The researchers failed to find any benefit in regard to neurological outcomes or mortality. In VF OHCA, they observed a survival rate to hospital discharge of 62.7 % (intervention group) and 64.3% (controls). In the patients without VF, those rates were 19.2 and 16.3, respectively.

Neurological outcomes were also similar for patients with VF at 57.5% (intervention group) and 61.9% (controls), respectively. The non-VF rates were 14.4% (intervention) and 13.4 % (controls). Hypothermia was associated with significant adverse events, including pulmonary edema and increased use of diuretics.

These observations are contrary to previous observations and should provide an opportunity to reevaluate hypothermia for OHCA. These patients represent a series of complex metabolic issues that deserve careful research to provide answers to some of the outstanding issues. The recent studies provide an environment of equipoise where we can step back and revaluate this complex procedure in randomized control trials.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

In the last 30 years, there have been immense advances in the treatment and prevention of sudden cardiac arrest, including beta-blocker therapy and automatic implantable cardiac defibrillators.

In addition, communities have organized emergency medical systems (EMS) designed to provide early cardiac care for the prevention and treatment of cardiac arrest occurring outside the hospital (OHCA). One of the great frustrations of physicians working in the EMS environment is the successful cardiac resuscitation for the patient who is left with severe neurological impairment or brain death. It is clear that resuscitation of the brain is very time dependent. Complete interruption of blood flow to the brain leads to the loss of consciousness within seconds and death of vulnerable neurons in several brain regions occurs within minutes, whereas 20-40 minutes of ischemia is required to kill cardiac myocytes.

To improve survival and prevent the neurological sequelae of OHCA, total body hypothermia is advised based on animal laboratory experiments and a few small clinical studies carried out in a total of 179 OHCA patients (N. Engl. J. Med. 2002;346:557-63 and 549-56).

Both studies show both a neurological and survival benefit – particularly in patients resuscitated from ventricular fibrillation – in comatose patients in whom resuscitation was achieved within 5-10 minutes after witnessed cardiac arrest when cooled to 32-34 degrees Celsius within 60 minutes of collapse. These studies led to the recommendation by the International Liaison Committee on Resuscitation (Circulation 2004;110;3385-97) that cooling to 32-34 degrees Celsius for 12-24 hours should be used in unconscious patients with OHCA with VF and possibly non-VF arrests.

These recommendations were supported by the AHA Guideline Committee (Circulation 2010;122:S768-86) As a result, cooling comatose OHCA patients after resuscitation is widely used in emergency departments in the United States and Europe with the use of a variety of devices and techniques including large volume saline, external cooling devices, intravenous catheter devices, and intranasal devices. When hypothermia was initially recommended, a number of questions were unanswered and remain unanswered despite multiple publications and wide clinical experience in the succeeding 12 years. Some of those questions include the timing, duration, and intensity of cooling, the preferable technique of cooling, and risk and benefits of the different cooling techniques.

In the United States, pressure infusion of 2 liters of ice cold saline is the usual initial method of cooling to 32-34 degrees Celsius followed by 12-36 hours with surface cooling.

Investigators in Seattle randomized OHCA patients prior to hypothermia or standard therapy with both VF and non-VF rhythms before hospitalization to improve the previous reported benefit when initiated in hospital (JAMA 2014;311;45-52).

The initiation of prehospital therapy achieved cooling 1 hour earlier than in previous hospitalization studies. The result in 1,359 OHCAs over a 5-year period raises important questions about the benefit of hypothermia. The researchers failed to find any benefit in regard to neurological outcomes or mortality. In VF OHCA, they observed a survival rate to hospital discharge of 62.7 % (intervention group) and 64.3% (controls). In the patients without VF, those rates were 19.2 and 16.3, respectively.

Neurological outcomes were also similar for patients with VF at 57.5% (intervention group) and 61.9% (controls), respectively. The non-VF rates were 14.4% (intervention) and 13.4 % (controls). Hypothermia was associated with significant adverse events, including pulmonary edema and increased use of diuretics.

These observations are contrary to previous observations and should provide an opportunity to reevaluate hypothermia for OHCA. These patients represent a series of complex metabolic issues that deserve careful research to provide answers to some of the outstanding issues. The recent studies provide an environment of equipoise where we can step back and revaluate this complex procedure in randomized control trials.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

In the last 30 years, there have been immense advances in the treatment and prevention of sudden cardiac arrest, including beta-blocker therapy and automatic implantable cardiac defibrillators.

In addition, communities have organized emergency medical systems (EMS) designed to provide early cardiac care for the prevention and treatment of cardiac arrest occurring outside the hospital (OHCA). One of the great frustrations of physicians working in the EMS environment is the successful cardiac resuscitation for the patient who is left with severe neurological impairment or brain death. It is clear that resuscitation of the brain is very time dependent. Complete interruption of blood flow to the brain leads to the loss of consciousness within seconds and death of vulnerable neurons in several brain regions occurs within minutes, whereas 20-40 minutes of ischemia is required to kill cardiac myocytes.

To improve survival and prevent the neurological sequelae of OHCA, total body hypothermia is advised based on animal laboratory experiments and a few small clinical studies carried out in a total of 179 OHCA patients (N. Engl. J. Med. 2002;346:557-63 and 549-56).

Both studies show both a neurological and survival benefit – particularly in patients resuscitated from ventricular fibrillation – in comatose patients in whom resuscitation was achieved within 5-10 minutes after witnessed cardiac arrest when cooled to 32-34 degrees Celsius within 60 minutes of collapse. These studies led to the recommendation by the International Liaison Committee on Resuscitation (Circulation 2004;110;3385-97) that cooling to 32-34 degrees Celsius for 12-24 hours should be used in unconscious patients with OHCA with VF and possibly non-VF arrests.

These recommendations were supported by the AHA Guideline Committee (Circulation 2010;122:S768-86) As a result, cooling comatose OHCA patients after resuscitation is widely used in emergency departments in the United States and Europe with the use of a variety of devices and techniques including large volume saline, external cooling devices, intravenous catheter devices, and intranasal devices. When hypothermia was initially recommended, a number of questions were unanswered and remain unanswered despite multiple publications and wide clinical experience in the succeeding 12 years. Some of those questions include the timing, duration, and intensity of cooling, the preferable technique of cooling, and risk and benefits of the different cooling techniques.

In the United States, pressure infusion of 2 liters of ice cold saline is the usual initial method of cooling to 32-34 degrees Celsius followed by 12-36 hours with surface cooling.

Investigators in Seattle randomized OHCA patients prior to hypothermia or standard therapy with both VF and non-VF rhythms before hospitalization to improve the previous reported benefit when initiated in hospital (JAMA 2014;311;45-52).

The initiation of prehospital therapy achieved cooling 1 hour earlier than in previous hospitalization studies. The result in 1,359 OHCAs over a 5-year period raises important questions about the benefit of hypothermia. The researchers failed to find any benefit in regard to neurological outcomes or mortality. In VF OHCA, they observed a survival rate to hospital discharge of 62.7 % (intervention group) and 64.3% (controls). In the patients without VF, those rates were 19.2 and 16.3, respectively.

Neurological outcomes were also similar for patients with VF at 57.5% (intervention group) and 61.9% (controls), respectively. The non-VF rates were 14.4% (intervention) and 13.4 % (controls). Hypothermia was associated with significant adverse events, including pulmonary edema and increased use of diuretics.

These observations are contrary to previous observations and should provide an opportunity to reevaluate hypothermia for OHCA. These patients represent a series of complex metabolic issues that deserve careful research to provide answers to some of the outstanding issues. The recent studies provide an environment of equipoise where we can step back and revaluate this complex procedure in randomized control trials.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

The controversial hypertension-management guidelines released by the former JNC 8 panel in December was not the group’s last word. There was a minority report, too, published almost a month later in mid-January.

Five of the 17 members of the group originally assembled in 2008 by the National Heart, Lung, and Blood Institute (NHLBI) to research and write the eighth edition of the official U.S. hypertension guidelines not only disagreed with their 12 colleagues about resetting the systolic blood pressure target to 150 mm Hg from the prior target of 140 mm Hg for people aged 60-79 without diabetes or chronic kidney disease, but also felt strongly enough to write an article about it.

Courtesy Michael V. Hayes, Wikimedia Commons

A published minority report is not how most medical guideline writing panels usually work.

The history of the Eighth Joint National Committee (JNC 8) already featured some unusual twists. After many months of unexpected delays leading up to the report’s release, the NHLBI announced last June that it would hand off the JNC 8 process to an appropriate medical group. A few weeks later, the institute announced that JNC 8 would get published under the auspices of the American Heart Association and American College of Cardiology. Then came word that the arrangement had fallen through, leaving what became the former JNC 8 panel to release its data analysis and recommendations without endorsement from a medical association.

The fact that the 150–mm Hg systolic target for treating 60- to 79-year-olds was controversial among the panel members themselves was no surprise. The former JNC 8 panel’s majority report in December acknowledged their lack of consensus on this issue. What had been previously unknown was exactly how the panel split, and the minority view that led to the disagreement.

The five dissenters were Dr. Jackson T. Wright Jr., Case Medical Center, Cleveland; Dr. Lawrence J. Fine, NHLBI, Bethesda, Md.; Daniel T. Lackland, Ph.D., Medical University of South Carolina, Charleston; Dr. Gbenga Ogedegbe, New York University; and Cheryl R. Dennison Himmelfarb, Ph.D., Johns Hopkins University, Baltimore.

Summarizing their view in their report, the five said they "believed that evidence was insufficient to increase the SBP goal from its current level of less than 140 mm Hg because of concern that increasing the goal may cause harm by increasing the risk for CVD and partially undoing the remarkable progress in reducing cardiovascular mortality in Americans older than 60 years. Because of the overall evidence, including the RCT data reviewed by the panel, and the decrease in CVD mortality, we concluded that the evidence for increasing a blood pressure target in high-risk populations should be at least as strong as the evidence required to decrease the recommended blood pressure target. In addition, one target would simplify implementation for clinicians."

The unusual circumstances that surrounded release of the former JNC 8 panel’s report and the controversial systolic target they set initially raised questions about the impact the recommendations would have on U.S. practice. The minority report puts an asterisk on the majority report and dilutes its influence even more.

[email protected]

On Twitter @mitchelzoler

The controversial hypertension-management guidelines released by the former JNC 8 panel in December was not the group’s last word. There was a minority report, too, published almost a month later in mid-January.

Five of the 17 members of the group originally assembled in 2008 by the National Heart, Lung, and Blood Institute (NHLBI) to research and write the eighth edition of the official U.S. hypertension guidelines not only disagreed with their 12 colleagues about resetting the systolic blood pressure target to 150 mm Hg from the prior target of 140 mm Hg for people aged 60-79 without diabetes or chronic kidney disease, but also felt strongly enough to write an article about it.

Courtesy Michael V. Hayes, Wikimedia Commons

A published minority report is not how most medical guideline writing panels usually work.

The history of the Eighth Joint National Committee (JNC 8) already featured some unusual twists. After many months of unexpected delays leading up to the report’s release, the NHLBI announced last June that it would hand off the JNC 8 process to an appropriate medical group. A few weeks later, the institute announced that JNC 8 would get published under the auspices of the American Heart Association and American College of Cardiology. Then came word that the arrangement had fallen through, leaving what became the former JNC 8 panel to release its data analysis and recommendations without endorsement from a medical association.

The fact that the 150–mm Hg systolic target for treating 60- to 79-year-olds was controversial among the panel members themselves was no surprise. The former JNC 8 panel’s majority report in December acknowledged their lack of consensus on this issue. What had been previously unknown was exactly how the panel split, and the minority view that led to the disagreement.

The five dissenters were Dr. Jackson T. Wright Jr., Case Medical Center, Cleveland; Dr. Lawrence J. Fine, NHLBI, Bethesda, Md.; Daniel T. Lackland, Ph.D., Medical University of South Carolina, Charleston; Dr. Gbenga Ogedegbe, New York University; and Cheryl R. Dennison Himmelfarb, Ph.D., Johns Hopkins University, Baltimore.

Summarizing their view in their report, the five said they "believed that evidence was insufficient to increase the SBP goal from its current level of less than 140 mm Hg because of concern that increasing the goal may cause harm by increasing the risk for CVD and partially undoing the remarkable progress in reducing cardiovascular mortality in Americans older than 60 years. Because of the overall evidence, including the RCT data reviewed by the panel, and the decrease in CVD mortality, we concluded that the evidence for increasing a blood pressure target in high-risk populations should be at least as strong as the evidence required to decrease the recommended blood pressure target. In addition, one target would simplify implementation for clinicians."

The unusual circumstances that surrounded release of the former JNC 8 panel’s report and the controversial systolic target they set initially raised questions about the impact the recommendations would have on U.S. practice. The minority report puts an asterisk on the majority report and dilutes its influence even more.

[email protected]

On Twitter @mitchelzoler

The controversial hypertension-management guidelines released by the former JNC 8 panel in December was not the group’s last word. There was a minority report, too, published almost a month later in mid-January.

Five of the 17 members of the group originally assembled in 2008 by the National Heart, Lung, and Blood Institute (NHLBI) to research and write the eighth edition of the official U.S. hypertension guidelines not only disagreed with their 12 colleagues about resetting the systolic blood pressure target to 150 mm Hg from the prior target of 140 mm Hg for people aged 60-79 without diabetes or chronic kidney disease, but also felt strongly enough to write an article about it.

Courtesy Michael V. Hayes, Wikimedia Commons

A published minority report is not how most medical guideline writing panels usually work.

The history of the Eighth Joint National Committee (JNC 8) already featured some unusual twists. After many months of unexpected delays leading up to the report’s release, the NHLBI announced last June that it would hand off the JNC 8 process to an appropriate medical group. A few weeks later, the institute announced that JNC 8 would get published under the auspices of the American Heart Association and American College of Cardiology. Then came word that the arrangement had fallen through, leaving what became the former JNC 8 panel to release its data analysis and recommendations without endorsement from a medical association.

The fact that the 150–mm Hg systolic target for treating 60- to 79-year-olds was controversial among the panel members themselves was no surprise. The former JNC 8 panel’s majority report in December acknowledged their lack of consensus on this issue. What had been previously unknown was exactly how the panel split, and the minority view that led to the disagreement.

The five dissenters were Dr. Jackson T. Wright Jr., Case Medical Center, Cleveland; Dr. Lawrence J. Fine, NHLBI, Bethesda, Md.; Daniel T. Lackland, Ph.D., Medical University of South Carolina, Charleston; Dr. Gbenga Ogedegbe, New York University; and Cheryl R. Dennison Himmelfarb, Ph.D., Johns Hopkins University, Baltimore.

Summarizing their view in their report, the five said they "believed that evidence was insufficient to increase the SBP goal from its current level of less than 140 mm Hg because of concern that increasing the goal may cause harm by increasing the risk for CVD and partially undoing the remarkable progress in reducing cardiovascular mortality in Americans older than 60 years. Because of the overall evidence, including the RCT data reviewed by the panel, and the decrease in CVD mortality, we concluded that the evidence for increasing a blood pressure target in high-risk populations should be at least as strong as the evidence required to decrease the recommended blood pressure target. In addition, one target would simplify implementation for clinicians."

The unusual circumstances that surrounded release of the former JNC 8 panel’s report and the controversial systolic target they set initially raised questions about the impact the recommendations would have on U.S. practice. The minority report puts an asterisk on the majority report and dilutes its influence even more.

[email protected]

On Twitter @mitchelzoler

SAN FRANCISCO—Unlike its predecessors, a new prognostic model suggests race and histology are important predictors of outcome in patients with peripheral T-cell lymphoma (PTCL).

Researchers analyzed nearly 9000 patients diagnosed with PTCL in the US and found evidence to suggest that patient age and race, as well as histology and disease stage can be used to predict overall survival (OS).

The group’s findings also suggested the use of radiation is associated with improved OS. And later diagnosis may be associated with favorable outcome.

Adam M. Petrich, MD, of Northwestern University in Chicago, presented this research at the 6th Annual T-cell Lymphoma Forum, which took place January 23-25. Dr Petrich was 1 of 2 speakers to receive a Young Investigator Award for his presentation.

Dr Petrich noted that at least 5 models have been used to predict outcomes in patients with newly diagnosed PTCL—the International Prognostic Index (IPI), the Prognostic Index for PTCL (PIT), the International PTCL Project model (IPTCLP), the modified Prognostic Index for T-cell Lymphoma (mPIT), and the Extranodal Natural Killer/T Cell Lymphoma (ENKTL) model.

But these models have limitations, including small patient numbers and issues with applicability. So Dr Petrich and his colleagues wanted to take a closer look at prognostic factors in PTCL, to determine which factors from previously published models remain relevant.

Patient characteristics

The researchers used data from the SEER database, which included 20 state and local registries and captured 28% of the US population. There were 8802 cases of PTCL diagnosed between 2000 and 2010.

Patients ranged in age from 20 to 85 years, and 59% were male. With regard to race, 77% of patients were white, 13% were black, 9% were classified as “other,” and 1% were of unknown race.

Forty-eight percent of patients had stage I-II disease, 31% had stage III-IV, and the stage was unknown for 21% of patients. Extranodal disease was absent in 60% of patients, present in 26%, and unknown in 14%.

Histologies were as follows:

• 38.1% of patients had PTCL-not otherwise specified (PTCL-NOS)
• 24.2% had anaplastic large-cell lymphoma (ALCL)
• 12.7% had angioimmunoblastic T-cell lymphoma (AITL)
• 9.3% had adult T-cell leukemia/lymphoma (ATLL)
• 6.9% had extranodal NK/T-cell lymphoma (ENKTL)
• 3.2% had T-cell-prolymphocytic leukemia(T-PLL)
• 2.5% had T-cell large granular lymphocytic leukemia (T-LGL)
• 1.2% had subcutaneous panniculitis-like T-cell lymphoma (SCPTCL)
• 1.1% had enteropathy-associated T-cell lymphoma (EATL)
• 0.6% had hepatosplenic T-cell lymphoma (HSTL).

Prognostic factors revealed

The researchers performed univariate and multivariate analyses to determine the importance of the aforementioned factors on OS.

“We decided, since we have a large number of patients, to use a very stringent P value,” Dr Petrich said. “Only those that are less than 0.0001 were considered significant.”

In univariate analysis, age, race, disease stage, extranodal disease, use of radiation, and histology all significantly impacted OS. But in multivariate analysis, only race, age, histology, and disease stage retained significance.

“Extranodal disease is associated with protection from overall survival, but that P value did not reach significance (P=0.009),” Dr Petrich said.

Likewise, patients diagnosed from 2009 to 2010 had better OS than patients diagnosed from 2000 to 2008, but this did not meet the significance criterion (P=0.0002).

On the other hand, OS was significantly worse for black patients compared to white patients. And compared to patients aged 20-24, those 55 years of age and older had a significantly increased risk of death.

Compared to patients with PTCL-NOS, those with EATL, ENKTL, and T-LGL all had significantly worse OS. And patients with advanced-stage disease had significantly worse OS.

The researchers also looked at the use of radiation and found that it had a significant impact on survival.

“Of course, this isn’t a pre-treatment variable, but we did add it as sort of an exploratory analysis,” Dr Petrich said. “And regardless of disease stage, [radiation] seems to be associated with improved survival. But when we include it in a multivariate analysis, it’s also highly associated with protection from 5-year mortality (P<0.0001).”

Creating, validating the prognostic model

Dr Petrich and his colleagues created a prognostic model based on some of the aforementioned factors. They assigned points according to hazard ratios (HRs).

Patients received 1 point for each of the following factors: age 55 or older (HR 1.51), black race (HR 1.43), distant-stage disease (HR 1.79), PTCL-NOS (reference), AITL (HR 1.19), ALCL (HR 0.88), and ATLL (HR 1.34).

Patients received 2 points for each of the following histologies: HSTL (HR 1.76), EATL (HR 2.32), ENKTL (HR 1.50), and T-PLL (HR couldn’t be calculated). And they received 0 points for SCPTL (HR 0.71) and T-LGL (HR 0.43).

The researchers then applied the model to the population of 8802 patients and evaluated survival. The median OS was more than 120 months for patients with a score of 0-1, 36 months for those with a score of 2, 14 months for those with a score of 3, and 9 months for those with score of 4 or 5.

“We have good discrimination of outcome based on this scoring system, with patients with the most favorable prognosis having median survival that’s out over 10 years,” Dr Petrich said.

The researchers also obtained good discrimination when they tested the model in a validation cohort of 112 patients, Dr Petrich said. He noted, however, that validating the model with a larger patient population would provide better results.

He also pointed out that this study had its limitations, such as missing data and a lack of uniformity with regard to treatment. But the research does reveal factors that are likely important prognostic indicators in PTCL.

SAN FRANCISCO—Unlike its predecessors, a new prognostic model suggests race and histology are important predictors of outcome in patients with peripheral T-cell lymphoma (PTCL).

Researchers analyzed nearly 9000 patients diagnosed with PTCL in the US and found evidence to suggest that patient age and race, as well as histology and disease stage can be used to predict overall survival (OS).

The group’s findings also suggested the use of radiation is associated with improved OS. And later diagnosis may be associated with favorable outcome.

Adam M. Petrich, MD, of Northwestern University in Chicago, presented this research at the 6th Annual T-cell Lymphoma Forum, which took place January 23-25. Dr Petrich was 1 of 2 speakers to receive a Young Investigator Award for his presentation.

Dr Petrich noted that at least 5 models have been used to predict outcomes in patients with newly diagnosed PTCL—the International Prognostic Index (IPI), the Prognostic Index for PTCL (PIT), the International PTCL Project model (IPTCLP), the modified Prognostic Index for T-cell Lymphoma (mPIT), and the Extranodal Natural Killer/T Cell Lymphoma (ENKTL) model.

But these models have limitations, including small patient numbers and issues with applicability. So Dr Petrich and his colleagues wanted to take a closer look at prognostic factors in PTCL, to determine which factors from previously published models remain relevant.

Patient characteristics

The researchers used data from the SEER database, which included 20 state and local registries and captured 28% of the US population. There were 8802 cases of PTCL diagnosed between 2000 and 2010.

Patients ranged in age from 20 to 85 years, and 59% were male. With regard to race, 77% of patients were white, 13% were black, 9% were classified as “other,” and 1% were of unknown race.

Forty-eight percent of patients had stage I-II disease, 31% had stage III-IV, and the stage was unknown for 21% of patients. Extranodal disease was absent in 60% of patients, present in 26%, and unknown in 14%.

Histologies were as follows:

• 38.1% of patients had PTCL-not otherwise specified (PTCL-NOS)
• 24.2% had anaplastic large-cell lymphoma (ALCL)
• 12.7% had angioimmunoblastic T-cell lymphoma (AITL)
• 9.3% had adult T-cell leukemia/lymphoma (ATLL)
• 6.9% had extranodal NK/T-cell lymphoma (ENKTL)
• 3.2% had T-cell-prolymphocytic leukemia(T-PLL)
• 2.5% had T-cell large granular lymphocytic leukemia (T-LGL)
• 1.2% had subcutaneous panniculitis-like T-cell lymphoma (SCPTCL)
• 1.1% had enteropathy-associated T-cell lymphoma (EATL)
• 0.6% had hepatosplenic T-cell lymphoma (HSTL).

Prognostic factors revealed

The researchers performed univariate and multivariate analyses to determine the importance of the aforementioned factors on OS.

“We decided, since we have a large number of patients, to use a very stringent P value,” Dr Petrich said. “Only those that are less than 0.0001 were considered significant.”

In univariate analysis, age, race, disease stage, extranodal disease, use of radiation, and histology all significantly impacted OS. But in multivariate analysis, only race, age, histology, and disease stage retained significance.

“Extranodal disease is associated with protection from overall survival, but that P value did not reach significance (P=0.009),” Dr Petrich said.

Likewise, patients diagnosed from 2009 to 2010 had better OS than patients diagnosed from 2000 to 2008, but this did not meet the significance criterion (P=0.0002).

On the other hand, OS was significantly worse for black patients compared to white patients. And compared to patients aged 20-24, those 55 years of age and older had a significantly increased risk of death.

Compared to patients with PTCL-NOS, those with EATL, ENKTL, and T-LGL all had significantly worse OS. And patients with advanced-stage disease had significantly worse OS.

The researchers also looked at the use of radiation and found that it had a significant impact on survival.

“Of course, this isn’t a pre-treatment variable, but we did add it as sort of an exploratory analysis,” Dr Petrich said. “And regardless of disease stage, [radiation] seems to be associated with improved survival. But when we include it in a multivariate analysis, it’s also highly associated with protection from 5-year mortality (P<0.0001).”

Creating, validating the prognostic model

Dr Petrich and his colleagues created a prognostic model based on some of the aforementioned factors. They assigned points according to hazard ratios (HRs).

Patients received 1 point for each of the following factors: age 55 or older (HR 1.51), black race (HR 1.43), distant-stage disease (HR 1.79), PTCL-NOS (reference), AITL (HR 1.19), ALCL (HR 0.88), and ATLL (HR 1.34).

Patients received 2 points for each of the following histologies: HSTL (HR 1.76), EATL (HR 2.32), ENKTL (HR 1.50), and T-PLL (HR couldn’t be calculated). And they received 0 points for SCPTL (HR 0.71) and T-LGL (HR 0.43).

The researchers then applied the model to the population of 8802 patients and evaluated survival. The median OS was more than 120 months for patients with a score of 0-1, 36 months for those with a score of 2, 14 months for those with a score of 3, and 9 months for those with score of 4 or 5.

“We have good discrimination of outcome based on this scoring system, with patients with the most favorable prognosis having median survival that’s out over 10 years,” Dr Petrich said.

The researchers also obtained good discrimination when they tested the model in a validation cohort of 112 patients, Dr Petrich said. He noted, however, that validating the model with a larger patient population would provide better results.

He also pointed out that this study had its limitations, such as missing data and a lack of uniformity with regard to treatment. But the research does reveal factors that are likely important prognostic indicators in PTCL.

SAN FRANCISCO—Unlike its predecessors, a new prognostic model suggests race and histology are important predictors of outcome in patients with peripheral T-cell lymphoma (PTCL).

Researchers analyzed nearly 9000 patients diagnosed with PTCL in the US and found evidence to suggest that patient age and race, as well as histology and disease stage can be used to predict overall survival (OS).

The group’s findings also suggested the use of radiation is associated with improved OS. And later diagnosis may be associated with favorable outcome.

Adam M. Petrich, MD, of Northwestern University in Chicago, presented this research at the 6th Annual T-cell Lymphoma Forum, which took place January 23-25. Dr Petrich was 1 of 2 speakers to receive a Young Investigator Award for his presentation.

Dr Petrich noted that at least 5 models have been used to predict outcomes in patients with newly diagnosed PTCL—the International Prognostic Index (IPI), the Prognostic Index for PTCL (PIT), the International PTCL Project model (IPTCLP), the modified Prognostic Index for T-cell Lymphoma (mPIT), and the Extranodal Natural Killer/T Cell Lymphoma (ENKTL) model.

But these models have limitations, including small patient numbers and issues with applicability. So Dr Petrich and his colleagues wanted to take a closer look at prognostic factors in PTCL, to determine which factors from previously published models remain relevant.

Patient characteristics

The researchers used data from the SEER database, which included 20 state and local registries and captured 28% of the US population. There were 8802 cases of PTCL diagnosed between 2000 and 2010.

Patients ranged in age from 20 to 85 years, and 59% were male. With regard to race, 77% of patients were white, 13% were black, 9% were classified as “other,” and 1% were of unknown race.

Forty-eight percent of patients had stage I-II disease, 31% had stage III-IV, and the stage was unknown for 21% of patients. Extranodal disease was absent in 60% of patients, present in 26%, and unknown in 14%.

Histologies were as follows:

• 38.1% of patients had PTCL-not otherwise specified (PTCL-NOS)
• 24.2% had anaplastic large-cell lymphoma (ALCL)
• 12.7% had angioimmunoblastic T-cell lymphoma (AITL)
• 9.3% had adult T-cell leukemia/lymphoma (ATLL)
• 6.9% had extranodal NK/T-cell lymphoma (ENKTL)
• 3.2% had T-cell-prolymphocytic leukemia(T-PLL)
• 2.5% had T-cell large granular lymphocytic leukemia (T-LGL)
• 1.2% had subcutaneous panniculitis-like T-cell lymphoma (SCPTCL)
• 1.1% had enteropathy-associated T-cell lymphoma (EATL)
• 0.6% had hepatosplenic T-cell lymphoma (HSTL).

Prognostic factors revealed

The researchers performed univariate and multivariate analyses to determine the importance of the aforementioned factors on OS.

“We decided, since we have a large number of patients, to use a very stringent P value,” Dr Petrich said. “Only those that are less than 0.0001 were considered significant.”

In univariate analysis, age, race, disease stage, extranodal disease, use of radiation, and histology all significantly impacted OS. But in multivariate analysis, only race, age, histology, and disease stage retained significance.

“Extranodal disease is associated with protection from overall survival, but that P value did not reach significance (P=0.009),” Dr Petrich said.

Likewise, patients diagnosed from 2009 to 2010 had better OS than patients diagnosed from 2000 to 2008, but this did not meet the significance criterion (P=0.0002).

On the other hand, OS was significantly worse for black patients compared to white patients. And compared to patients aged 20-24, those 55 years of age and older had a significantly increased risk of death.

Compared to patients with PTCL-NOS, those with EATL, ENKTL, and T-LGL all had significantly worse OS. And patients with advanced-stage disease had significantly worse OS.

The researchers also looked at the use of radiation and found that it had a significant impact on survival.

“Of course, this isn’t a pre-treatment variable, but we did add it as sort of an exploratory analysis,” Dr Petrich said. “And regardless of disease stage, [radiation] seems to be associated with improved survival. But when we include it in a multivariate analysis, it’s also highly associated with protection from 5-year mortality (P<0.0001).”

Creating, validating the prognostic model

Dr Petrich and his colleagues created a prognostic model based on some of the aforementioned factors. They assigned points according to hazard ratios (HRs).

Patients received 1 point for each of the following factors: age 55 or older (HR 1.51), black race (HR 1.43), distant-stage disease (HR 1.79), PTCL-NOS (reference), AITL (HR 1.19), ALCL (HR 0.88), and ATLL (HR 1.34).

Patients received 2 points for each of the following histologies: HSTL (HR 1.76), EATL (HR 2.32), ENKTL (HR 1.50), and T-PLL (HR couldn’t be calculated). And they received 0 points for SCPTL (HR 0.71) and T-LGL (HR 0.43).

The researchers then applied the model to the population of 8802 patients and evaluated survival. The median OS was more than 120 months for patients with a score of 0-1, 36 months for those with a score of 2, 14 months for those with a score of 3, and 9 months for those with score of 4 or 5.

“We have good discrimination of outcome based on this scoring system, with patients with the most favorable prognosis having median survival that’s out over 10 years,” Dr Petrich said.

The researchers also obtained good discrimination when they tested the model in a validation cohort of 112 patients, Dr Petrich said. He noted, however, that validating the model with a larger patient population would provide better results.

He also pointed out that this study had its limitations, such as missing data and a lack of uniformity with regard to treatment. But the research does reveal factors that are likely important prognostic indicators in PTCL.

HSCs in the bone marrow

Scientists have long thought that hematopoietic stem cells (HSCs) are regulated similarly in males and females.

But research conducted in mice has shown that HSCs exhibit sex differences in cell-cycle regulation.

The researchers discovered that HSCs in female mice divided significantly more frequently than HSCs in male mice, and this appeared to be driven by estrogen.

Sean Morrison, PhD, of UT Southwestern Medical Center in Dallas, and his colleagues detailed these discoveries in a letter to Nature.

The research suggested that differences in HSC division depend on the ovaries and not the testes. When the investigators administered estradiol, a hormone produced mainly in the ovaries, to male and female mice, HSC division increased in both sexes.

And experiments in pregnant mice highlighted the importance of estrogen in HSC activity. Estrogen levels increased during pregnancy, which increased HSC division, HSC frequency, cellularity, and erythropoiesis in the spleen.

“Elevated estrogen levels that are sustained during pregnancy induce stem cell mobilization and red cell production in the spleen, which serves as a reserve site for additional red blood cell production,” Dr Morrison said.

He and his colleagues also found that HSCs expressed high levels of estrogen receptor-alpha. And deleting the receptor reduced HSC division in female mice but not in males.

In pregnant mice, deleting the receptor attenuated the previously observed increases in HSC division, HSC frequency, and erythropoiesis.

These results suggest estrogen acts directly on HSCs to increase their proliferation and the number of red blood cells they generate.

“If estrogen has the same effect on stem cells in humans as in mice, then this effect raises a number of possibilities that could change the way we treat people with diseases of blood cell formation,” Dr Morrison said.

“Can we promote regeneration in the blood-forming system by administering estrogen? Can we reduce the toxicity of chemotherapy to the blood-forming system by taking into account estrogen levels in female patients? Does estrogen promote the growth of some blood cancers? There are numerous clinical opportunities to pursue.”

HSCs in the bone marrow

Scientists have long thought that hematopoietic stem cells (HSCs) are regulated similarly in males and females.

But research conducted in mice has shown that HSCs exhibit sex differences in cell-cycle regulation.

The researchers discovered that HSCs in female mice divided significantly more frequently than HSCs in male mice, and this appeared to be driven by estrogen.

Sean Morrison, PhD, of UT Southwestern Medical Center in Dallas, and his colleagues detailed these discoveries in a letter to Nature.

The research suggested that differences in HSC division depend on the ovaries and not the testes. When the investigators administered estradiol, a hormone produced mainly in the ovaries, to male and female mice, HSC division increased in both sexes.

And experiments in pregnant mice highlighted the importance of estrogen in HSC activity. Estrogen levels increased during pregnancy, which increased HSC division, HSC frequency, cellularity, and erythropoiesis in the spleen.

“Elevated estrogen levels that are sustained during pregnancy induce stem cell mobilization and red cell production in the spleen, which serves as a reserve site for additional red blood cell production,” Dr Morrison said.

He and his colleagues also found that HSCs expressed high levels of estrogen receptor-alpha. And deleting the receptor reduced HSC division in female mice but not in males.

In pregnant mice, deleting the receptor attenuated the previously observed increases in HSC division, HSC frequency, and erythropoiesis.

These results suggest estrogen acts directly on HSCs to increase their proliferation and the number of red blood cells they generate.

“If estrogen has the same effect on stem cells in humans as in mice, then this effect raises a number of possibilities that could change the way we treat people with diseases of blood cell formation,” Dr Morrison said.

“Can we promote regeneration in the blood-forming system by administering estrogen? Can we reduce the toxicity of chemotherapy to the blood-forming system by taking into account estrogen levels in female patients? Does estrogen promote the growth of some blood cancers? There are numerous clinical opportunities to pursue.”

HSCs in the bone marrow

Scientists have long thought that hematopoietic stem cells (HSCs) are regulated similarly in males and females.

But research conducted in mice has shown that HSCs exhibit sex differences in cell-cycle regulation.

The researchers discovered that HSCs in female mice divided significantly more frequently than HSCs in male mice, and this appeared to be driven by estrogen.

Sean Morrison, PhD, of UT Southwestern Medical Center in Dallas, and his colleagues detailed these discoveries in a letter to Nature.

The research suggested that differences in HSC division depend on the ovaries and not the testes. When the investigators administered estradiol, a hormone produced mainly in the ovaries, to male and female mice, HSC division increased in both sexes.

And experiments in pregnant mice highlighted the importance of estrogen in HSC activity. Estrogen levels increased during pregnancy, which increased HSC division, HSC frequency, cellularity, and erythropoiesis in the spleen.

“Elevated estrogen levels that are sustained during pregnancy induce stem cell mobilization and red cell production in the spleen, which serves as a reserve site for additional red blood cell production,” Dr Morrison said.

He and his colleagues also found that HSCs expressed high levels of estrogen receptor-alpha. And deleting the receptor reduced HSC division in female mice but not in males.

In pregnant mice, deleting the receptor attenuated the previously observed increases in HSC division, HSC frequency, and erythropoiesis.

These results suggest estrogen acts directly on HSCs to increase their proliferation and the number of red blood cells they generate.

“If estrogen has the same effect on stem cells in humans as in mice, then this effect raises a number of possibilities that could change the way we treat people with diseases of blood cell formation,” Dr Morrison said.

“Can we promote regeneration in the blood-forming system by administering estrogen? Can we reduce the toxicity of chemotherapy to the blood-forming system by taking into account estrogen levels in female patients? Does estrogen promote the growth of some blood cancers? There are numerous clinical opportunities to pursue.”

Cancer patient

Credit: Bill Branson

Childhood cancer patients are no more likely than their healthy peers to develop post-traumatic stress disorder (PTSD), according to research published in the Journal of Clinical Oncology.

“A cancer diagnosis is a highly significant and challenging event, but this study highlights the impressive capacity of children to adjust to changes in their lives and, in most cases, do just fine or even thrive emotionally as a result,” said study author Sean Phipps, PhD, of St Jude Children’s Research Hospital in Memphis.

PTSD is a treatable anxiety disorder that can develop following terrifying events that result in real or potential physical harm. The diagnosis is based on patient reports of certain symptoms, including persistent frightening thoughts, flashbacks, numbness, detachment, and sleep disturbances.

For this study, researchers used 3 established PTSD screening methods on 255 pediatric cancer patients (aged 8 to 17 at diagnosis) and 101 of their healthy, demographically matched peers.

This included a symptom check list and a structured diagnostic interview about the event in a child’s life he or she identified as the most traumatic. The researchers also interviewed parents about PTSD symptoms in themselves and their children.

Based on self-reported symptoms, 2.8% of cancer patients (n=7) met the criteria for a diagnosis of PTSD, either when the study was conducted or in the past.

The PTSD was cancer-related in 2 of these patients. In the other 5 patients, the disorder was linked to a drive-by shooting, Hurricane Katrina, or other stressful events.

By diagnostic interview, 0.4% of the cancer patients met PTSD criteria. According to parents’ reports, 1.6% of the cancer patients met criteria for current PTSD, and 5.9% met lifetime criteria.

These rates of PTSD were not significantly different from the rates reported in the healthy control subjects (all P values were greater than 0.1).

Unlike many previous studies of PTSD in cancer patients, researchers initially refrained from asking patients specifically about their diagnosis. Investigators wanted to avoid suggesting to patients that their cancer diagnoses were traumatic.

“We know such suggestions, called ‘focusing illusions,’ prime individuals to think about their cancer experience as traumatic and leaves them prone to exaggerating its impact in subjective reports,” Dr Phipps said.

Cancer patient

Credit: Bill Branson

Childhood cancer patients are no more likely than their healthy peers to develop post-traumatic stress disorder (PTSD), according to research published in the Journal of Clinical Oncology.

“A cancer diagnosis is a highly significant and challenging event, but this study highlights the impressive capacity of children to adjust to changes in their lives and, in most cases, do just fine or even thrive emotionally as a result,” said study author Sean Phipps, PhD, of St Jude Children’s Research Hospital in Memphis.

PTSD is a treatable anxiety disorder that can develop following terrifying events that result in real or potential physical harm. The diagnosis is based on patient reports of certain symptoms, including persistent frightening thoughts, flashbacks, numbness, detachment, and sleep disturbances.

For this study, researchers used 3 established PTSD screening methods on 255 pediatric cancer patients (aged 8 to 17 at diagnosis) and 101 of their healthy, demographically matched peers.

This included a symptom check list and a structured diagnostic interview about the event in a child’s life he or she identified as the most traumatic. The researchers also interviewed parents about PTSD symptoms in themselves and their children.

Based on self-reported symptoms, 2.8% of cancer patients (n=7) met the criteria for a diagnosis of PTSD, either when the study was conducted or in the past.

The PTSD was cancer-related in 2 of these patients. In the other 5 patients, the disorder was linked to a drive-by shooting, Hurricane Katrina, or other stressful events.

By diagnostic interview, 0.4% of the cancer patients met PTSD criteria. According to parents’ reports, 1.6% of the cancer patients met criteria for current PTSD, and 5.9% met lifetime criteria.

These rates of PTSD were not significantly different from the rates reported in the healthy control subjects (all P values were greater than 0.1).

Unlike many previous studies of PTSD in cancer patients, researchers initially refrained from asking patients specifically about their diagnosis. Investigators wanted to avoid suggesting to patients that their cancer diagnoses were traumatic.

“We know such suggestions, called ‘focusing illusions,’ prime individuals to think about their cancer experience as traumatic and leaves them prone to exaggerating its impact in subjective reports,” Dr Phipps said.

Cancer patient

Credit: Bill Branson

Childhood cancer patients are no more likely than their healthy peers to develop post-traumatic stress disorder (PTSD), according to research published in the Journal of Clinical Oncology.

“A cancer diagnosis is a highly significant and challenging event, but this study highlights the impressive capacity of children to adjust to changes in their lives and, in most cases, do just fine or even thrive emotionally as a result,” said study author Sean Phipps, PhD, of St Jude Children’s Research Hospital in Memphis.

PTSD is a treatable anxiety disorder that can develop following terrifying events that result in real or potential physical harm. The diagnosis is based on patient reports of certain symptoms, including persistent frightening thoughts, flashbacks, numbness, detachment, and sleep disturbances.

For this study, researchers used 3 established PTSD screening methods on 255 pediatric cancer patients (aged 8 to 17 at diagnosis) and 101 of their healthy, demographically matched peers.

This included a symptom check list and a structured diagnostic interview about the event in a child’s life he or she identified as the most traumatic. The researchers also interviewed parents about PTSD symptoms in themselves and their children.

Based on self-reported symptoms, 2.8% of cancer patients (n=7) met the criteria for a diagnosis of PTSD, either when the study was conducted or in the past.

The PTSD was cancer-related in 2 of these patients. In the other 5 patients, the disorder was linked to a drive-by shooting, Hurricane Katrina, or other stressful events.

By diagnostic interview, 0.4% of the cancer patients met PTSD criteria. According to parents’ reports, 1.6% of the cancer patients met criteria for current PTSD, and 5.9% met lifetime criteria.

These rates of PTSD were not significantly different from the rates reported in the healthy control subjects (all P values were greater than 0.1).

Unlike many previous studies of PTSD in cancer patients, researchers initially refrained from asking patients specifically about their diagnosis. Investigators wanted to avoid suggesting to patients that their cancer diagnoses were traumatic.

“We know such suggestions, called ‘focusing illusions,’ prime individuals to think about their cancer experience as traumatic and leaves them prone to exaggerating its impact in subjective reports,” Dr Phipps said.

Doctor consults with a family

Credit: Rhoda Baer

Previous research has indicated that requiring conflict of interest (COI) disclosures may lead advisers to give more biased advice.

However, virtually all of the prior studies questioned the effectiveness of COI disclosures that advisers were unable to avoid.

With a new study, researchers examined situations in which advisers have the ability to avoid COIs—such as doctors who can decide whether to accept gifts or payments from pharmaceutical companies.

And the results showed that when COIs can be avoided, disclosure successfully deters advisers from accepting COIs, so they have nothing to disclose except the absence of conflicts.

The research was published in Psychological Science.

“Prior research has cast doubt as to the effectiveness of disclosure for managing conflicts of interest, particularly when consumers have the burden of interpreting and reacting to the information,” said study author Sunita Sah, PhD, MB ChB, of Georgetown University in Washington, DC.

“Our findings suggest that disclosure can become a successful intervention to managing some conflicts of interest if it motivates professionals or providers to avoid such conflicts.”

For this study, the researchers conducted 3 experiments to determine how COIs influence advisers. In the first experiment, 97 adviser–advisee pairs participated in an online game with Amazon.com gift cards at stake.

Advisers informed the advisees regarding the number of filled dots on a grid. The estimators were paid based on their accuracy, but advisers had a conflict. They were paid more if advisees gave an estimate that was higher than the true value.

The set up—with advisees only seeing a small subset of the complete grid—was designed to simulate a situation in which a consumer receives advice from a better-informed but conflicted professional. The results replicated previous research and showed that disclosure led advisers to give higher (and more biased) recommendations than nondisclosure.

In the second experiment, the researchers again randomly assigned pairs of advisees and advisers to conditions in which the conflict was either disclosed or not disclosed.

There was, however, an important change from the first study. Advisers were given a choice of whether to accept or reject the COI.

Without disclosure, a majority of advisers (63%) chose the incentives that created a COI. But with disclosure, a minority (33%) accepted the conflict.

Advice was higher (and more biased) for those who chose incentives with conflicts than for those who did not, and advisers in the disclosure condition gave significantly less biased advice than those in the nondisclosure condition.

Finally, in a study with 248 participants, the researchers added a third condition to the second experiment: voluntary disclosure. In this third condition, advisers decided both whether to choose incentives that entailed a conflict and whether to disclose if they had a conflict.

Similar to mandatory disclosure, voluntary disclosure led advisers to avoid COIs and then disclose their freedom from conflicts to advisees.

“Disclosure doesn’t seem to be much good when conflicts are unavoidable, but it does seem to help when advisers have a choice about whether to subject themselves to conflicts,” said study author George Loewenstein, PhD, of Carnegie Mellon University in Pittsburgh.

“A nice feature of disclosure is that it is, in effect, ‘self-calibrating.’ Doctors, for example, are unlikely to find it worth it to accept small gifts such as pens or calendars if the gifts are going to be disclosed. Although larger gifts would be more tempting, doctors are likely to be deterred from accepting them because disclosure of large gifts would be more damaging to their reputations.”

Doctor consults with a family

Credit: Rhoda Baer

Previous research has indicated that requiring conflict of interest (COI) disclosures may lead advisers to give more biased advice.

However, virtually all of the prior studies questioned the effectiveness of COI disclosures that advisers were unable to avoid.

With a new study, researchers examined situations in which advisers have the ability to avoid COIs—such as doctors who can decide whether to accept gifts or payments from pharmaceutical companies.

And the results showed that when COIs can be avoided, disclosure successfully deters advisers from accepting COIs, so they have nothing to disclose except the absence of conflicts.

The research was published in Psychological Science.

“Prior research has cast doubt as to the effectiveness of disclosure for managing conflicts of interest, particularly when consumers have the burden of interpreting and reacting to the information,” said study author Sunita Sah, PhD, MB ChB, of Georgetown University in Washington, DC.

“Our findings suggest that disclosure can become a successful intervention to managing some conflicts of interest if it motivates professionals or providers to avoid such conflicts.”

For this study, the researchers conducted 3 experiments to determine how COIs influence advisers. In the first experiment, 97 adviser–advisee pairs participated in an online game with Amazon.com gift cards at stake.

Advisers informed the advisees regarding the number of filled dots on a grid. The estimators were paid based on their accuracy, but advisers had a conflict. They were paid more if advisees gave an estimate that was higher than the true value.

The set up—with advisees only seeing a small subset of the complete grid—was designed to simulate a situation in which a consumer receives advice from a better-informed but conflicted professional. The results replicated previous research and showed that disclosure led advisers to give higher (and more biased) recommendations than nondisclosure.

In the second experiment, the researchers again randomly assigned pairs of advisees and advisers to conditions in which the conflict was either disclosed or not disclosed.

There was, however, an important change from the first study. Advisers were given a choice of whether to accept or reject the COI.

Without disclosure, a majority of advisers (63%) chose the incentives that created a COI. But with disclosure, a minority (33%) accepted the conflict.

Advice was higher (and more biased) for those who chose incentives with conflicts than for those who did not, and advisers in the disclosure condition gave significantly less biased advice than those in the nondisclosure condition.

Finally, in a study with 248 participants, the researchers added a third condition to the second experiment: voluntary disclosure. In this third condition, advisers decided both whether to choose incentives that entailed a conflict and whether to disclose if they had a conflict.

Similar to mandatory disclosure, voluntary disclosure led advisers to avoid COIs and then disclose their freedom from conflicts to advisees.

“Disclosure doesn’t seem to be much good when conflicts are unavoidable, but it does seem to help when advisers have a choice about whether to subject themselves to conflicts,” said study author George Loewenstein, PhD, of Carnegie Mellon University in Pittsburgh.

“A nice feature of disclosure is that it is, in effect, ‘self-calibrating.’ Doctors, for example, are unlikely to find it worth it to accept small gifts such as pens or calendars if the gifts are going to be disclosed. Although larger gifts would be more tempting, doctors are likely to be deterred from accepting them because disclosure of large gifts would be more damaging to their reputations.”

Doctor consults with a family

Credit: Rhoda Baer

Previous research has indicated that requiring conflict of interest (COI) disclosures may lead advisers to give more biased advice.

However, virtually all of the prior studies questioned the effectiveness of COI disclosures that advisers were unable to avoid.

With a new study, researchers examined situations in which advisers have the ability to avoid COIs—such as doctors who can decide whether to accept gifts or payments from pharmaceutical companies.

And the results showed that when COIs can be avoided, disclosure successfully deters advisers from accepting COIs, so they have nothing to disclose except the absence of conflicts.

The research was published in Psychological Science.

“Prior research has cast doubt as to the effectiveness of disclosure for managing conflicts of interest, particularly when consumers have the burden of interpreting and reacting to the information,” said study author Sunita Sah, PhD, MB ChB, of Georgetown University in Washington, DC.

“Our findings suggest that disclosure can become a successful intervention to managing some conflicts of interest if it motivates professionals or providers to avoid such conflicts.”

For this study, the researchers conducted 3 experiments to determine how COIs influence advisers. In the first experiment, 97 adviser–advisee pairs participated in an online game with Amazon.com gift cards at stake.

Advisers informed the advisees regarding the number of filled dots on a grid. The estimators were paid based on their accuracy, but advisers had a conflict. They were paid more if advisees gave an estimate that was higher than the true value.

The set up—with advisees only seeing a small subset of the complete grid—was designed to simulate a situation in which a consumer receives advice from a better-informed but conflicted professional. The results replicated previous research and showed that disclosure led advisers to give higher (and more biased) recommendations than nondisclosure.

In the second experiment, the researchers again randomly assigned pairs of advisees and advisers to conditions in which the conflict was either disclosed or not disclosed.

There was, however, an important change from the first study. Advisers were given a choice of whether to accept or reject the COI.

Without disclosure, a majority of advisers (63%) chose the incentives that created a COI. But with disclosure, a minority (33%) accepted the conflict.

Advice was higher (and more biased) for those who chose incentives with conflicts than for those who did not, and advisers in the disclosure condition gave significantly less biased advice than those in the nondisclosure condition.

Finally, in a study with 248 participants, the researchers added a third condition to the second experiment: voluntary disclosure. In this third condition, advisers decided both whether to choose incentives that entailed a conflict and whether to disclose if they had a conflict.

Similar to mandatory disclosure, voluntary disclosure led advisers to avoid COIs and then disclose their freedom from conflicts to advisees.

“Disclosure doesn’t seem to be much good when conflicts are unavoidable, but it does seem to help when advisers have a choice about whether to subject themselves to conflicts,” said study author George Loewenstein, PhD, of Carnegie Mellon University in Pittsburgh.

“A nice feature of disclosure is that it is, in effect, ‘self-calibrating.’ Doctors, for example, are unlikely to find it worth it to accept small gifts such as pens or calendars if the gifts are going to be disclosed. Although larger gifts would be more tempting, doctors are likely to be deterred from accepting them because disclosure of large gifts would be more damaging to their reputations.”

Since FDA approval of endovascular aneurysm repair in 1999, the management of abdominal aortic aneurysms has transformed. Only 5.2% of AAAs were repaired by EVAR in 2000 compared to 74% in 2010. While the volume of AAA cases has remained constant at about 45,000 cases annually, the increase in EVAR has led to a 34% drop in open AAA cases. This national decline in open AAA cases is paralleled by a 33% decline in open AAA cases completed by vascular trainees since 2001, as reported in national Accreditation Council for Graduate Medical Education case logs.

In conjunction with this decrease in open AAA repair volume, trainees are reporting low confidence in independently performing open aneurysm cases, with nearly 40% of 2014 graduating vascular trainees having expressed low confidence in their ability on a 3-point Likert scale (1 – not confident, 2 – somewhat confident, 3 – very confident).

Over the past decade, we have also seen a threefold increase in adjudicated cases against vascular surgeons due to complications arising from open AAA cases, along with an increase in litigation against vascular surgeons who have been in practice for fewer than 3 years.

Open AAA surgery volume will continue to decrease as branched and fenestrated technology improves, and as expanded utilization in patients with complex anatomy occurs with the next generation of endografts.

By 2020, based on prediction models, vascular trainees will complete only five open aneurysm cases during their training, This raises serious questions about how we will educate the next generation of vascular surgeons to safely and effectively manage patients who can be treated only by open repair.

Since FDA approval of endovascular aneurysm repair in 1999, the management of abdominal aortic aneurysms has transformed. Only 5.2% of AAAs were repaired by EVAR in 2000 compared to 74% in 2010. While the volume of AAA cases has remained constant at about 45,000 cases annually, the increase in EVAR has led to a 34% drop in open AAA cases. This national decline in open AAA cases is paralleled by a 33% decline in open AAA cases completed by vascular trainees since 2001, as reported in national Accreditation Council for Graduate Medical Education case logs.

In conjunction with this decrease in open AAA repair volume, trainees are reporting low confidence in independently performing open aneurysm cases, with nearly 40% of 2014 graduating vascular trainees having expressed low confidence in their ability on a 3-point Likert scale (1 – not confident, 2 – somewhat confident, 3 – very confident).

Over the past decade, we have also seen a threefold increase in adjudicated cases against vascular surgeons due to complications arising from open AAA cases, along with an increase in litigation against vascular surgeons who have been in practice for fewer than 3 years.

Open AAA surgery volume will continue to decrease as branched and fenestrated technology improves, and as expanded utilization in patients with complex anatomy occurs with the next generation of endografts.

By 2020, based on prediction models, vascular trainees will complete only five open aneurysm cases during their training, This raises serious questions about how we will educate the next generation of vascular surgeons to safely and effectively manage patients who can be treated only by open repair.

Since FDA approval of endovascular aneurysm repair in 1999, the management of abdominal aortic aneurysms has transformed. Only 5.2% of AAAs were repaired by EVAR in 2000 compared to 74% in 2010. While the volume of AAA cases has remained constant at about 45,000 cases annually, the increase in EVAR has led to a 34% drop in open AAA cases. This national decline in open AAA cases is paralleled by a 33% decline in open AAA cases completed by vascular trainees since 2001, as reported in national Accreditation Council for Graduate Medical Education case logs.

In conjunction with this decrease in open AAA repair volume, trainees are reporting low confidence in independently performing open aneurysm cases, with nearly 40% of 2014 graduating vascular trainees having expressed low confidence in their ability on a 3-point Likert scale (1 – not confident, 2 – somewhat confident, 3 – very confident).

Over the past decade, we have also seen a threefold increase in adjudicated cases against vascular surgeons due to complications arising from open AAA cases, along with an increase in litigation against vascular surgeons who have been in practice for fewer than 3 years.

Open AAA surgery volume will continue to decrease as branched and fenestrated technology improves, and as expanded utilization in patients with complex anatomy occurs with the next generation of endografts.

By 2020, based on prediction models, vascular trainees will complete only five open aneurysm cases during their training, This raises serious questions about how we will educate the next generation of vascular surgeons to safely and effectively manage patients who can be treated only by open repair.