Bruce Jancin

SAN ANTONIO – Gene expression profile testing to guide decisions regarding the use of adjuvant chemotherapy for early-stage breast cancer should not be used to override the results of standard pathologic measures, Dr. Antonio C. Wolff asserted at the annual San Antonio Breast Cancer Symposium.

Two gene expression profile tests commonly used in breast cancer are the Oncotype DX and MammaPrint assays. The excitement surrounding this whole field is such that Dr. Wolff suspects many clinicians see the molecular assays as being superior to standard clinicopathologic data in their predictive information. This actually hasn’t been shown to be the case to date, he stressed.

"One of the big messages I bring today is that one method is not necessarily better than the other. The standard pathologic tests and the molecular assays may be complementary in the information they provide," said Dr. Wolff, professor of oncology at Johns Hopkins University, Baltimore.

He added that while guideline-based use of these first-generation molecular assays as recommended by the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the European St. Gallen’s Expert Consensus group is appropriate, it’s important to recognize that these tests have their shortcomings. For one, they leave a lot of patients in the gray intermediate-risk zone. Also, the tests aren’t applicable to the 25%-35% of breast cancer patients with estrogen receptor–negative tumors. But a host of new technologies are in the pipeline, he observed.

A recent study of 7,375 breast cancer patients with hormone receptor–positive breast cancer diagnosed in 2006-2008 was enlightening with regard to how clinicians are using gene expression profile testing. The study, an analysis of NCCN prospective registry data conducted by investigators at Boston’s Dana-Farber Cancer Institute, showed a progressive increase in the use of the Oncotype DX test. The test was employed in 14.7% of the patients diagnosed in 2006, nearly doubling to 27.5% of those diagnosed in 2008. Meanwhile, use of chemotherapy decreased from 53.9% to 47%.

Gene expression profile testing was associated with an overall 30% reduction in the likelihood of receiving chemotherapy. What Dr. Wolff found particularly interesting was that testing of small, node-negative cancers was associated with an 11.1-fold increased likelihood of chemotherapy, while testing of lymph node–positive or large node-negative cancers was associated with an 89% reduction in chemotherapy (J. Clin. Oncol. 2012;30:2218-26).

African American women were 30% less likely to undergo testing. Women with no more than a high school education were 37% less likely to be tested than were those with more schooling. Dr. Wolff suspects these disparities are a reflection of better-educated women asking more questions of their physician about their planned treatment course, and the physician in response seeking more laboratory data to help in making treatment decisions.

Dr. Wolff said that while clinicians await studies to determine whether molecular and standard clinicopathologic information can be combined to improve prediction, one of the most important things they can do is to pay close attention to preanalytic issues.

"It’s critical to get tissue from patient to pathologist within 1 hour to avoid cold ischemia and necrosis and deterioration of the specimen that will not only adversely affect the quality of standard measures, but also of the new measures. This is a big deal!" he emphasized.

Dr. Wolff reported that he serves as an investigator for Genentech.

SAN ANTONIO – Gene expression profile testing to guide decisions regarding the use of adjuvant chemotherapy for early-stage breast cancer should not be used to override the results of standard pathologic measures, Dr. Antonio C. Wolff asserted at the annual San Antonio Breast Cancer Symposium.

Two gene expression profile tests commonly used in breast cancer are the Oncotype DX and MammaPrint assays. The excitement surrounding this whole field is such that Dr. Wolff suspects many clinicians see the molecular assays as being superior to standard clinicopathologic data in their predictive information. This actually hasn’t been shown to be the case to date, he stressed.

"One of the big messages I bring today is that one method is not necessarily better than the other. The standard pathologic tests and the molecular assays may be complementary in the information they provide," said Dr. Wolff, professor of oncology at Johns Hopkins University, Baltimore.

He added that while guideline-based use of these first-generation molecular assays as recommended by the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the European St. Gallen’s Expert Consensus group is appropriate, it’s important to recognize that these tests have their shortcomings. For one, they leave a lot of patients in the gray intermediate-risk zone. Also, the tests aren’t applicable to the 25%-35% of breast cancer patients with estrogen receptor–negative tumors. But a host of new technologies are in the pipeline, he observed.

A recent study of 7,375 breast cancer patients with hormone receptor–positive breast cancer diagnosed in 2006-2008 was enlightening with regard to how clinicians are using gene expression profile testing. The study, an analysis of NCCN prospective registry data conducted by investigators at Boston’s Dana-Farber Cancer Institute, showed a progressive increase in the use of the Oncotype DX test. The test was employed in 14.7% of the patients diagnosed in 2006, nearly doubling to 27.5% of those diagnosed in 2008. Meanwhile, use of chemotherapy decreased from 53.9% to 47%.

Gene expression profile testing was associated with an overall 30% reduction in the likelihood of receiving chemotherapy. What Dr. Wolff found particularly interesting was that testing of small, node-negative cancers was associated with an 11.1-fold increased likelihood of chemotherapy, while testing of lymph node–positive or large node-negative cancers was associated with an 89% reduction in chemotherapy (J. Clin. Oncol. 2012;30:2218-26).

African American women were 30% less likely to undergo testing. Women with no more than a high school education were 37% less likely to be tested than were those with more schooling. Dr. Wolff suspects these disparities are a reflection of better-educated women asking more questions of their physician about their planned treatment course, and the physician in response seeking more laboratory data to help in making treatment decisions.

Dr. Wolff said that while clinicians await studies to determine whether molecular and standard clinicopathologic information can be combined to improve prediction, one of the most important things they can do is to pay close attention to preanalytic issues.

"It’s critical to get tissue from patient to pathologist within 1 hour to avoid cold ischemia and necrosis and deterioration of the specimen that will not only adversely affect the quality of standard measures, but also of the new measures. This is a big deal!" he emphasized.

Dr. Wolff reported that he serves as an investigator for Genentech.

SAN ANTONIO – Gene expression profile testing to guide decisions regarding the use of adjuvant chemotherapy for early-stage breast cancer should not be used to override the results of standard pathologic measures, Dr. Antonio C. Wolff asserted at the annual San Antonio Breast Cancer Symposium.

Two gene expression profile tests commonly used in breast cancer are the Oncotype DX and MammaPrint assays. The excitement surrounding this whole field is such that Dr. Wolff suspects many clinicians see the molecular assays as being superior to standard clinicopathologic data in their predictive information. This actually hasn’t been shown to be the case to date, he stressed.

"One of the big messages I bring today is that one method is not necessarily better than the other. The standard pathologic tests and the molecular assays may be complementary in the information they provide," said Dr. Wolff, professor of oncology at Johns Hopkins University, Baltimore.

He added that while guideline-based use of these first-generation molecular assays as recommended by the American Society of Clinical Oncology (ASCO), the National Comprehensive Cancer Network (NCCN), and the European St. Gallen’s Expert Consensus group is appropriate, it’s important to recognize that these tests have their shortcomings. For one, they leave a lot of patients in the gray intermediate-risk zone. Also, the tests aren’t applicable to the 25%-35% of breast cancer patients with estrogen receptor–negative tumors. But a host of new technologies are in the pipeline, he observed.

A recent study of 7,375 breast cancer patients with hormone receptor–positive breast cancer diagnosed in 2006-2008 was enlightening with regard to how clinicians are using gene expression profile testing. The study, an analysis of NCCN prospective registry data conducted by investigators at Boston’s Dana-Farber Cancer Institute, showed a progressive increase in the use of the Oncotype DX test. The test was employed in 14.7% of the patients diagnosed in 2006, nearly doubling to 27.5% of those diagnosed in 2008. Meanwhile, use of chemotherapy decreased from 53.9% to 47%.

Gene expression profile testing was associated with an overall 30% reduction in the likelihood of receiving chemotherapy. What Dr. Wolff found particularly interesting was that testing of small, node-negative cancers was associated with an 11.1-fold increased likelihood of chemotherapy, while testing of lymph node–positive or large node-negative cancers was associated with an 89% reduction in chemotherapy (J. Clin. Oncol. 2012;30:2218-26).

African American women were 30% less likely to undergo testing. Women with no more than a high school education were 37% less likely to be tested than were those with more schooling. Dr. Wolff suspects these disparities are a reflection of better-educated women asking more questions of their physician about their planned treatment course, and the physician in response seeking more laboratory data to help in making treatment decisions.

Dr. Wolff said that while clinicians await studies to determine whether molecular and standard clinicopathologic information can be combined to improve prediction, one of the most important things they can do is to pay close attention to preanalytic issues.

"It’s critical to get tissue from patient to pathologist within 1 hour to avoid cold ischemia and necrosis and deterioration of the specimen that will not only adversely affect the quality of standard measures, but also of the new measures. This is a big deal!" he emphasized.

Dr. Wolff reported that he serves as an investigator for Genentech.

LOS ANGELES – Mechanical venovenous ultrafiltration proved inferior to drug therapy in diuretic-responsive patients hospitalized with acute decompensated heart failure and cardiorenal syndrome in a major multicenter randomized trial.

In the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF), weight loss due to elimination of excess fluid was similar at 96 hours in the two treatment arms. However, renal function was significantly worse in the ultrafiltration group at that time point, and it remained so even 60 days from baseline, Dr. Bradley A. Bart reported at the annual scientific sessions of the American Heart Association.

Moreover, the combined rate of the secondary end point comprising death or serious adverse events at 6 months was 72% in the ultrafiltration group, compared with 57% in patients treated with a standardized pharmacologic regimen, for an adjusted 50% increased risk in the ultrafiltration group. Serious adverse events included kidney failure, bleeding complications, and problems due to intravenous catheters.

"Neither group was adequately decongested at the time of hospital discharge. This is a challenging group of patients to treat. The 60-day event rates are very high, and better therapies are needed in the future," said Dr. Bart of the Hennepin County Medical Center, Minneapolis.

Acute cardiorenal syndrome occurs in up to one-third of patients with acute decompensated heart failure. The CARRESS-HF trial randomized 188 affected patients who were diuretic responsive to a stepped pharmacologic care algorithm or to ultrafiltration at a rate of 200 mL/hr using the commercially available Aquadex System 100 device manufactured by CHF Solutions.

Both treatment groups lost about 12 pounds through 96 hours. However, while mean serum creatinine was unchanged from baseline in the drug therapy group, it climbed by 0.25 mg/dL in the ultrafiltration group.

Discussant Dr. Milton Packer agreed with the investigators’ conclusion that the study data offer no support for the use of mechanical ultrafiltration in patients who are responsive to diuretics.

"I still think there’s a role for ultrafiltration in patients who are diuretic unresponsive," added Dr. Packer, professor and chairman of the department of clinical sciences at the University of Texas Southwestern Medical Center, Dallas.

He called CARRESS-HF "a really terrific study and an important one." Ultrafiltration can be programmed to pull fluid off of patients more rapidly than is possible with drug therapy. Had mechanical ultrafiltration performed better than well-managed drug therapy in CARRESS-HF, the message to physicians would have been that they shouldn’t spend much time fiddling with diuretic therapy in such patients, but should instead turn to ultrafiltration much earlier during the hospitalization, even in diuretic-responsive patients.

"What is striking about this study is that the difference in renal function was present not only during the ultrafiltration but afterward. That’s something that, frankly speaking, gives us pause. It may be worthwhile in someone who’s diuretic unresponsive; it’s not worthwhile in someone who is diuretic responsive," according to Dr. Packer.

Simultaneous with Dr. Bart’s presentation of the CARRESS-HF results at the AHA conference, the study findings were published online (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1210357]).

In an accompanying editorial, Dr. W.H. Wilson Tang of the Cleveland Clinic called the outcomes in CARRESS-HF "overall dismal," with more than one-third of patients dying or being readmitted for acute decompensated heart failure within 60 days, regardless of their treatment arm. But that’s representative of what happens in everyday clinical practice when acute cardiorenal syndrome occurs (N. Engl. J. Med. 2012 [doi:10.1056/NEJMe1212881]).

It’s unclear why serum creatinine rose further and stayed high in the ultrafiltration-treated patients. Dr. Tang speculated that it might be because the mechanical device drew off fluid so rapidly that kidney perfusion was decreased.

"We may even have to confront the possibility that the pressure to reduce hospital length of stay with a strategy of initial aggressive diuresis in patients with acute decompensated heart failure may actually result in an increased incidence of the acute cardiorenal syndrome and cause unwanted consequences. Perhaps slow and steady may ultimately win the race after all," according to Dr. Tang.

CARRESS-HF was sponsored by the National Heart, Lung, and Blood Institute and carried out by the Heart Failure Clinical Research Network. Dr. Bart, Dr. Packer, and Dr. Tang reported having no relevant financial disclosures.

LOS ANGELES – Mechanical venovenous ultrafiltration proved inferior to drug therapy in diuretic-responsive patients hospitalized with acute decompensated heart failure and cardiorenal syndrome in a major multicenter randomized trial.

In the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF), weight loss due to elimination of excess fluid was similar at 96 hours in the two treatment arms. However, renal function was significantly worse in the ultrafiltration group at that time point, and it remained so even 60 days from baseline, Dr. Bradley A. Bart reported at the annual scientific sessions of the American Heart Association.

Moreover, the combined rate of the secondary end point comprising death or serious adverse events at 6 months was 72% in the ultrafiltration group, compared with 57% in patients treated with a standardized pharmacologic regimen, for an adjusted 50% increased risk in the ultrafiltration group. Serious adverse events included kidney failure, bleeding complications, and problems due to intravenous catheters.

"Neither group was adequately decongested at the time of hospital discharge. This is a challenging group of patients to treat. The 60-day event rates are very high, and better therapies are needed in the future," said Dr. Bart of the Hennepin County Medical Center, Minneapolis.

Acute cardiorenal syndrome occurs in up to one-third of patients with acute decompensated heart failure. The CARRESS-HF trial randomized 188 affected patients who were diuretic responsive to a stepped pharmacologic care algorithm or to ultrafiltration at a rate of 200 mL/hr using the commercially available Aquadex System 100 device manufactured by CHF Solutions.

Both treatment groups lost about 12 pounds through 96 hours. However, while mean serum creatinine was unchanged from baseline in the drug therapy group, it climbed by 0.25 mg/dL in the ultrafiltration group.

Discussant Dr. Milton Packer agreed with the investigators’ conclusion that the study data offer no support for the use of mechanical ultrafiltration in patients who are responsive to diuretics.

"I still think there’s a role for ultrafiltration in patients who are diuretic unresponsive," added Dr. Packer, professor and chairman of the department of clinical sciences at the University of Texas Southwestern Medical Center, Dallas.

He called CARRESS-HF "a really terrific study and an important one." Ultrafiltration can be programmed to pull fluid off of patients more rapidly than is possible with drug therapy. Had mechanical ultrafiltration performed better than well-managed drug therapy in CARRESS-HF, the message to physicians would have been that they shouldn’t spend much time fiddling with diuretic therapy in such patients, but should instead turn to ultrafiltration much earlier during the hospitalization, even in diuretic-responsive patients.

"What is striking about this study is that the difference in renal function was present not only during the ultrafiltration but afterward. That’s something that, frankly speaking, gives us pause. It may be worthwhile in someone who’s diuretic unresponsive; it’s not worthwhile in someone who is diuretic responsive," according to Dr. Packer.

Simultaneous with Dr. Bart’s presentation of the CARRESS-HF results at the AHA conference, the study findings were published online (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1210357]).

In an accompanying editorial, Dr. W.H. Wilson Tang of the Cleveland Clinic called the outcomes in CARRESS-HF "overall dismal," with more than one-third of patients dying or being readmitted for acute decompensated heart failure within 60 days, regardless of their treatment arm. But that’s representative of what happens in everyday clinical practice when acute cardiorenal syndrome occurs (N. Engl. J. Med. 2012 [doi:10.1056/NEJMe1212881]).

It’s unclear why serum creatinine rose further and stayed high in the ultrafiltration-treated patients. Dr. Tang speculated that it might be because the mechanical device drew off fluid so rapidly that kidney perfusion was decreased.

"We may even have to confront the possibility that the pressure to reduce hospital length of stay with a strategy of initial aggressive diuresis in patients with acute decompensated heart failure may actually result in an increased incidence of the acute cardiorenal syndrome and cause unwanted consequences. Perhaps slow and steady may ultimately win the race after all," according to Dr. Tang.

CARRESS-HF was sponsored by the National Heart, Lung, and Blood Institute and carried out by the Heart Failure Clinical Research Network. Dr. Bart, Dr. Packer, and Dr. Tang reported having no relevant financial disclosures.

LOS ANGELES – Mechanical venovenous ultrafiltration proved inferior to drug therapy in diuretic-responsive patients hospitalized with acute decompensated heart failure and cardiorenal syndrome in a major multicenter randomized trial.

In the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS-HF), weight loss due to elimination of excess fluid was similar at 96 hours in the two treatment arms. However, renal function was significantly worse in the ultrafiltration group at that time point, and it remained so even 60 days from baseline, Dr. Bradley A. Bart reported at the annual scientific sessions of the American Heart Association.

Moreover, the combined rate of the secondary end point comprising death or serious adverse events at 6 months was 72% in the ultrafiltration group, compared with 57% in patients treated with a standardized pharmacologic regimen, for an adjusted 50% increased risk in the ultrafiltration group. Serious adverse events included kidney failure, bleeding complications, and problems due to intravenous catheters.

"Neither group was adequately decongested at the time of hospital discharge. This is a challenging group of patients to treat. The 60-day event rates are very high, and better therapies are needed in the future," said Dr. Bart of the Hennepin County Medical Center, Minneapolis.

Acute cardiorenal syndrome occurs in up to one-third of patients with acute decompensated heart failure. The CARRESS-HF trial randomized 188 affected patients who were diuretic responsive to a stepped pharmacologic care algorithm or to ultrafiltration at a rate of 200 mL/hr using the commercially available Aquadex System 100 device manufactured by CHF Solutions.

Both treatment groups lost about 12 pounds through 96 hours. However, while mean serum creatinine was unchanged from baseline in the drug therapy group, it climbed by 0.25 mg/dL in the ultrafiltration group.

Discussant Dr. Milton Packer agreed with the investigators’ conclusion that the study data offer no support for the use of mechanical ultrafiltration in patients who are responsive to diuretics.

"I still think there’s a role for ultrafiltration in patients who are diuretic unresponsive," added Dr. Packer, professor and chairman of the department of clinical sciences at the University of Texas Southwestern Medical Center, Dallas.

He called CARRESS-HF "a really terrific study and an important one." Ultrafiltration can be programmed to pull fluid off of patients more rapidly than is possible with drug therapy. Had mechanical ultrafiltration performed better than well-managed drug therapy in CARRESS-HF, the message to physicians would have been that they shouldn’t spend much time fiddling with diuretic therapy in such patients, but should instead turn to ultrafiltration much earlier during the hospitalization, even in diuretic-responsive patients.

"What is striking about this study is that the difference in renal function was present not only during the ultrafiltration but afterward. That’s something that, frankly speaking, gives us pause. It may be worthwhile in someone who’s diuretic unresponsive; it’s not worthwhile in someone who is diuretic responsive," according to Dr. Packer.

Simultaneous with Dr. Bart’s presentation of the CARRESS-HF results at the AHA conference, the study findings were published online (N. Engl. J. Med. 2012 [doi:10.1056/NEJMoa1210357]).

In an accompanying editorial, Dr. W.H. Wilson Tang of the Cleveland Clinic called the outcomes in CARRESS-HF "overall dismal," with more than one-third of patients dying or being readmitted for acute decompensated heart failure within 60 days, regardless of their treatment arm. But that’s representative of what happens in everyday clinical practice when acute cardiorenal syndrome occurs (N. Engl. J. Med. 2012 [doi:10.1056/NEJMe1212881]).

It’s unclear why serum creatinine rose further and stayed high in the ultrafiltration-treated patients. Dr. Tang speculated that it might be because the mechanical device drew off fluid so rapidly that kidney perfusion was decreased.

"We may even have to confront the possibility that the pressure to reduce hospital length of stay with a strategy of initial aggressive diuresis in patients with acute decompensated heart failure may actually result in an increased incidence of the acute cardiorenal syndrome and cause unwanted consequences. Perhaps slow and steady may ultimately win the race after all," according to Dr. Tang.

CARRESS-HF was sponsored by the National Heart, Lung, and Blood Institute and carried out by the Heart Failure Clinical Research Network. Dr. Bart, Dr. Packer, and Dr. Tang reported having no relevant financial disclosures.

LOS ANGELES – Young adults with high blood pressure who regularly saw a primary care physician were substantially less likely to receive a hypertension diagnosis than were older affected patients – and some of the reasons for the greater delay in initial diagnosis are eye opening, said Dr. Heather M. Johnson.

The 18- to 31-year-olds met standard diagnostic criteria for hypertension. Their regularly elevated blood pressure measurements were dutifully entered into their medical records. Yet in a study conducted in a large multispecialty academic group practice, the majority of hypertensive young adults remained undiagnosed after 4 years of regular utilization of primary care, she reported at the annual scientific sessions of the American Heart Association.

That’s consistent with findings from other studies showing that young adults with hypertension have lower rates of diagnosis and hypertension control than middle-aged and elderly patients with high blood pressure, Dr. Johnson noted. Her study went farther, however, exploring possible explanations for the disparity.

The study involved analysis of the electronic medical records of 13,593 patients aged 18 years or older, all of whom regularly utilized primary care services during 2008-2011 and fulfilled national guideline–based criteria for the diagnosis of hypertension.

After 4 years of regular primary care, 67.4% of 18- to 24-year-olds with clear evidence of hypertension in their charts remained undiagnosed. So did 65% of affected 25- to 31-year-olds. These rates were significantly higher than in the older hypertensive patients seen in primary care.

Indeed, after 4 years, 18- to 24-year-olds with high blood pressure were 28% less likely to have received an initial hypertension diagnosis than were affected adults aged 60 years or older. Affected 25- to 31-year-olds were 26% less likely to have been diagnosed than patients aged 60 and up. These results were adjusted statistically for age, sex, race, body weight, primary spoken language, comorbid conditions, provider specialty, and other variables, explained Dr. Johnson, a cardiologist at the University of Wisconsin, Madison.

Rates of undiagnosed hypertension declined steadily with advancing age. Nonetheless, 54% of hypertensive patients aged 60 or older remained undiagnosed after 4 years, despite the objective evidence in their charts.

Intriguingly, the average time to diagnosis for patients whose hypertension was diagnosed within 4 years didn’t vary significantly by age: It was 5-6 months, regardless, she added.

Dr. Johnson pointed to provider, patient, and health care system factors as all being critical determinants of the poor rates of hypertension diagnosis among young adults.

One key independent predictor of delay to initial hypertension diagnosis in young adults identified in her multivariate analysis was patient race. Black young adults with hypertension were 39% more likely to have received the diagnosis than white patients.

"African Americans are known to have a higher prevalence of hypertension and its comorbidities, especially at younger age groups. Our data suggest providers are aware of this," Dr. Johnson said.

Young adults who were current users of tobacco or were regularly exposed to secondhand smoke were 29% less likely than never users to have their hypertension diagnosed.

Those with baseline blood pressures of 140-159/90-99 mm Hg were 35% less likely to receive a hypertension diagnosis within 4 years than those with baseline readings of 160-179/100-109 mm Hg.

On the provider side, physician gender emerged as a major independent predictor of delayed diagnosis in young adults. Female primary care providers were 23% more likely to promptly diagnose hypertension in affected young adults than were their male colleagues.

Family physicians were 16% less likely than general internists, ob.gyns., or other primary care providers to make the diagnosis in affected young adults. This was a finding of borderline statistical significance (P = 0.047), and Dr. Johnson said she doesn’t draw any strong conclusions from it.

She and her coworkers are conducting interviews with primary care providers in the group practice to learn how to improve hypertension diagnosis rates in young adults within the time constraints of a busy practice. The findings from this study will be used to develop tailored primary care interventions. This will entail provider education programs as well as upgraded electronic medical record notification systems.

Her work is funded by the National Heart, Lung, and Blood Institute. She reported having no relevant financial disclosures.

LOS ANGELES – Young adults with high blood pressure who regularly saw a primary care physician were substantially less likely to receive a hypertension diagnosis than were older affected patients – and some of the reasons for the greater delay in initial diagnosis are eye opening, said Dr. Heather M. Johnson.

The 18- to 31-year-olds met standard diagnostic criteria for hypertension. Their regularly elevated blood pressure measurements were dutifully entered into their medical records. Yet in a study conducted in a large multispecialty academic group practice, the majority of hypertensive young adults remained undiagnosed after 4 years of regular utilization of primary care, she reported at the annual scientific sessions of the American Heart Association.

That’s consistent with findings from other studies showing that young adults with hypertension have lower rates of diagnosis and hypertension control than middle-aged and elderly patients with high blood pressure, Dr. Johnson noted. Her study went farther, however, exploring possible explanations for the disparity.

The study involved analysis of the electronic medical records of 13,593 patients aged 18 years or older, all of whom regularly utilized primary care services during 2008-2011 and fulfilled national guideline–based criteria for the diagnosis of hypertension.

After 4 years of regular primary care, 67.4% of 18- to 24-year-olds with clear evidence of hypertension in their charts remained undiagnosed. So did 65% of affected 25- to 31-year-olds. These rates were significantly higher than in the older hypertensive patients seen in primary care.

Indeed, after 4 years, 18- to 24-year-olds with high blood pressure were 28% less likely to have received an initial hypertension diagnosis than were affected adults aged 60 years or older. Affected 25- to 31-year-olds were 26% less likely to have been diagnosed than patients aged 60 and up. These results were adjusted statistically for age, sex, race, body weight, primary spoken language, comorbid conditions, provider specialty, and other variables, explained Dr. Johnson, a cardiologist at the University of Wisconsin, Madison.

Rates of undiagnosed hypertension declined steadily with advancing age. Nonetheless, 54% of hypertensive patients aged 60 or older remained undiagnosed after 4 years, despite the objective evidence in their charts.

Intriguingly, the average time to diagnosis for patients whose hypertension was diagnosed within 4 years didn’t vary significantly by age: It was 5-6 months, regardless, she added.

Dr. Johnson pointed to provider, patient, and health care system factors as all being critical determinants of the poor rates of hypertension diagnosis among young adults.

One key independent predictor of delay to initial hypertension diagnosis in young adults identified in her multivariate analysis was patient race. Black young adults with hypertension were 39% more likely to have received the diagnosis than white patients.

"African Americans are known to have a higher prevalence of hypertension and its comorbidities, especially at younger age groups. Our data suggest providers are aware of this," Dr. Johnson said.

Young adults who were current users of tobacco or were regularly exposed to secondhand smoke were 29% less likely than never users to have their hypertension diagnosed.

Those with baseline blood pressures of 140-159/90-99 mm Hg were 35% less likely to receive a hypertension diagnosis within 4 years than those with baseline readings of 160-179/100-109 mm Hg.

On the provider side, physician gender emerged as a major independent predictor of delayed diagnosis in young adults. Female primary care providers were 23% more likely to promptly diagnose hypertension in affected young adults than were their male colleagues.

Family physicians were 16% less likely than general internists, ob.gyns., or other primary care providers to make the diagnosis in affected young adults. This was a finding of borderline statistical significance (P = 0.047), and Dr. Johnson said she doesn’t draw any strong conclusions from it.

She and her coworkers are conducting interviews with primary care providers in the group practice to learn how to improve hypertension diagnosis rates in young adults within the time constraints of a busy practice. The findings from this study will be used to develop tailored primary care interventions. This will entail provider education programs as well as upgraded electronic medical record notification systems.

Her work is funded by the National Heart, Lung, and Blood Institute. She reported having no relevant financial disclosures.

LOS ANGELES – Young adults with high blood pressure who regularly saw a primary care physician were substantially less likely to receive a hypertension diagnosis than were older affected patients – and some of the reasons for the greater delay in initial diagnosis are eye opening, said Dr. Heather M. Johnson.

The 18- to 31-year-olds met standard diagnostic criteria for hypertension. Their regularly elevated blood pressure measurements were dutifully entered into their medical records. Yet in a study conducted in a large multispecialty academic group practice, the majority of hypertensive young adults remained undiagnosed after 4 years of regular utilization of primary care, she reported at the annual scientific sessions of the American Heart Association.

That’s consistent with findings from other studies showing that young adults with hypertension have lower rates of diagnosis and hypertension control than middle-aged and elderly patients with high blood pressure, Dr. Johnson noted. Her study went farther, however, exploring possible explanations for the disparity.

The study involved analysis of the electronic medical records of 13,593 patients aged 18 years or older, all of whom regularly utilized primary care services during 2008-2011 and fulfilled national guideline–based criteria for the diagnosis of hypertension.

After 4 years of regular primary care, 67.4% of 18- to 24-year-olds with clear evidence of hypertension in their charts remained undiagnosed. So did 65% of affected 25- to 31-year-olds. These rates were significantly higher than in the older hypertensive patients seen in primary care.

Indeed, after 4 years, 18- to 24-year-olds with high blood pressure were 28% less likely to have received an initial hypertension diagnosis than were affected adults aged 60 years or older. Affected 25- to 31-year-olds were 26% less likely to have been diagnosed than patients aged 60 and up. These results were adjusted statistically for age, sex, race, body weight, primary spoken language, comorbid conditions, provider specialty, and other variables, explained Dr. Johnson, a cardiologist at the University of Wisconsin, Madison.

Rates of undiagnosed hypertension declined steadily with advancing age. Nonetheless, 54% of hypertensive patients aged 60 or older remained undiagnosed after 4 years, despite the objective evidence in their charts.

Intriguingly, the average time to diagnosis for patients whose hypertension was diagnosed within 4 years didn’t vary significantly by age: It was 5-6 months, regardless, she added.

Dr. Johnson pointed to provider, patient, and health care system factors as all being critical determinants of the poor rates of hypertension diagnosis among young adults.

One key independent predictor of delay to initial hypertension diagnosis in young adults identified in her multivariate analysis was patient race. Black young adults with hypertension were 39% more likely to have received the diagnosis than white patients.

"African Americans are known to have a higher prevalence of hypertension and its comorbidities, especially at younger age groups. Our data suggest providers are aware of this," Dr. Johnson said.

Young adults who were current users of tobacco or were regularly exposed to secondhand smoke were 29% less likely than never users to have their hypertension diagnosed.

Those with baseline blood pressures of 140-159/90-99 mm Hg were 35% less likely to receive a hypertension diagnosis within 4 years than those with baseline readings of 160-179/100-109 mm Hg.

On the provider side, physician gender emerged as a major independent predictor of delayed diagnosis in young adults. Female primary care providers were 23% more likely to promptly diagnose hypertension in affected young adults than were their male colleagues.

Family physicians were 16% less likely than general internists, ob.gyns., or other primary care providers to make the diagnosis in affected young adults. This was a finding of borderline statistical significance (P = 0.047), and Dr. Johnson said she doesn’t draw any strong conclusions from it.

She and her coworkers are conducting interviews with primary care providers in the group practice to learn how to improve hypertension diagnosis rates in young adults within the time constraints of a busy practice. The findings from this study will be used to develop tailored primary care interventions. This will entail provider education programs as well as upgraded electronic medical record notification systems.

Her work is funded by the National Heart, Lung, and Blood Institute. She reported having no relevant financial disclosures.

PRAGUE – Rates of three common malignancies – breast cancer, prostate cancer, and colorectal cancer – appear to be lower in psoriasis patients than in the general population of the Canadian maritime provinces of Newfoundland and Labrador, a study has shown.

In addition, only a single case of lymphoma occurred in 3,289 psoriasis patients followed for an average of 10 years, Dr. Wayne Gulliver said in presenting preliminary results of the ongoing study at the annual congress of the European Academy of Dermatology and Venereology.

The issue of a possible elevated risk of lymphoma in psoriasis patients has been controversial. Findings have been inconsistent. Some studies have reported a significantly increased risk. Among these, notably, was a population-based cohort study of more than 153,000 psoriasis patients and close to 800,000 controls in the U.K. General Practice Research Database. Investigators found an age- and sex-adjusted 35% increased risk of lymphoma in the group with psoriasis (J. Invest. Dermatol. 2006;126:2194-201).

However, lymphoma is an uncommon disease and a 35% increased risk is, from an epidemiologic perspective, only modest. Some studies have not found a significant association between psoriasis and lymphoma. The Canadian maritime study can be added to their ranks, according to Dr. Gulliver, professor of medicine and chairman of the division of dermatology at Memorial University of Newfoundland, St. John’s.

He matched records from a comprehensive research database of psoriasis patients in Newfoundland and Labrador for 1989-2010 with Canadian national and provincial cancer statistics. The purpose of the study was straightforward: "Our patients want to know if their psoriasis affects their risk of cancer, especially with the treatments we’re offering them these days," Dr. Gulliver said.

There were 232 cancer cases in 3,289 psoriasis patients, for a cumulative incidence rate of 588/100,000 population with psoriasis. Although the psoriasis population was divided nearly equally between men and women, 145 men developed cancer compared with 87 women.

Cancer rates were similar regardless of whether patients had mild psoriasis – meaning they received no systemic therapies – or moderate to severe psoriasis.

The cumulative incidence rate of breast cancer among psoriasis patients was 52/100,000 patients with mild psoriasis and 64/100,000 with moderate to severe disease compared with 96/100,000 in the general Canadian population and 84/100,000 among residents of Newfoundland and Labrador. The prostate cancer rate was 103/100,000 patients with mild psoriasis and 75/100,000 with moderate to severe psoriasis as opposed to 121/100,000 nationwide and 129/100,000 men in the general population of the two maritime provinces. The cumulative incidence rate for colorectal cancer followed the same pattern: lower in the psoriasis patients than in the general population.

Nonmelanoma skin cancer rates were relatively high: 142/100,000 patients with mild psoriasis and 122/100,000 with moderate to severe disease. That’s consistent with findings from other studies. It comes as no surprise given the common use of UV therapy and sunlight exposure in psoriasis patients.

Dr. Gulliver noted the relatively small number of cancers to date is a significant study limitation. But that number will grow as the psoriasis patients age; plus, more psoriasis patients are being added to the provincial database. He added that the database provides fertile ground for planned future studies. He said he plans soon to compare cancer rates in psoriasis patients on immunosuppressive therapy with biologic agents or cyclosporine to rates in patients on other agents.

One audience member observed that it seems more than coincidental that increased rates of breast, prostate, and colorectal cancers in the general population have previously been linked to low vitamin D levels. Perhaps the same factor that drives the increase in nonmelanoma skin cancer in psoriasis patients – that is, UV exposure – is responsible for their lower risks of those three common internal malignancies through a mechanism involving enhanced serum vitamin D levels, he speculated.

Dr. Gulliver called that a fascinating hypothesis and one he is now eager to investigate, since he has access to blood samples for the study population.

The study was free of commercial involvement, and the presenter reported having no relevant financial conflicts.

PRAGUE – Rates of three common malignancies – breast cancer, prostate cancer, and colorectal cancer – appear to be lower in psoriasis patients than in the general population of the Canadian maritime provinces of Newfoundland and Labrador, a study has shown.

In addition, only a single case of lymphoma occurred in 3,289 psoriasis patients followed for an average of 10 years, Dr. Wayne Gulliver said in presenting preliminary results of the ongoing study at the annual congress of the European Academy of Dermatology and Venereology.

The issue of a possible elevated risk of lymphoma in psoriasis patients has been controversial. Findings have been inconsistent. Some studies have reported a significantly increased risk. Among these, notably, was a population-based cohort study of more than 153,000 psoriasis patients and close to 800,000 controls in the U.K. General Practice Research Database. Investigators found an age- and sex-adjusted 35% increased risk of lymphoma in the group with psoriasis (J. Invest. Dermatol. 2006;126:2194-201).

However, lymphoma is an uncommon disease and a 35% increased risk is, from an epidemiologic perspective, only modest. Some studies have not found a significant association between psoriasis and lymphoma. The Canadian maritime study can be added to their ranks, according to Dr. Gulliver, professor of medicine and chairman of the division of dermatology at Memorial University of Newfoundland, St. John’s.

He matched records from a comprehensive research database of psoriasis patients in Newfoundland and Labrador for 1989-2010 with Canadian national and provincial cancer statistics. The purpose of the study was straightforward: "Our patients want to know if their psoriasis affects their risk of cancer, especially with the treatments we’re offering them these days," Dr. Gulliver said.

There were 232 cancer cases in 3,289 psoriasis patients, for a cumulative incidence rate of 588/100,000 population with psoriasis. Although the psoriasis population was divided nearly equally between men and women, 145 men developed cancer compared with 87 women.

Cancer rates were similar regardless of whether patients had mild psoriasis – meaning they received no systemic therapies – or moderate to severe psoriasis.

The cumulative incidence rate of breast cancer among psoriasis patients was 52/100,000 patients with mild psoriasis and 64/100,000 with moderate to severe disease compared with 96/100,000 in the general Canadian population and 84/100,000 among residents of Newfoundland and Labrador. The prostate cancer rate was 103/100,000 patients with mild psoriasis and 75/100,000 with moderate to severe psoriasis as opposed to 121/100,000 nationwide and 129/100,000 men in the general population of the two maritime provinces. The cumulative incidence rate for colorectal cancer followed the same pattern: lower in the psoriasis patients than in the general population.

Nonmelanoma skin cancer rates were relatively high: 142/100,000 patients with mild psoriasis and 122/100,000 with moderate to severe disease. That’s consistent with findings from other studies. It comes as no surprise given the common use of UV therapy and sunlight exposure in psoriasis patients.

Dr. Gulliver noted the relatively small number of cancers to date is a significant study limitation. But that number will grow as the psoriasis patients age; plus, more psoriasis patients are being added to the provincial database. He added that the database provides fertile ground for planned future studies. He said he plans soon to compare cancer rates in psoriasis patients on immunosuppressive therapy with biologic agents or cyclosporine to rates in patients on other agents.

One audience member observed that it seems more than coincidental that increased rates of breast, prostate, and colorectal cancers in the general population have previously been linked to low vitamin D levels. Perhaps the same factor that drives the increase in nonmelanoma skin cancer in psoriasis patients – that is, UV exposure – is responsible for their lower risks of those three common internal malignancies through a mechanism involving enhanced serum vitamin D levels, he speculated.

Dr. Gulliver called that a fascinating hypothesis and one he is now eager to investigate, since he has access to blood samples for the study population.

The study was free of commercial involvement, and the presenter reported having no relevant financial conflicts.

PRAGUE – Rates of three common malignancies – breast cancer, prostate cancer, and colorectal cancer – appear to be lower in psoriasis patients than in the general population of the Canadian maritime provinces of Newfoundland and Labrador, a study has shown.

In addition, only a single case of lymphoma occurred in 3,289 psoriasis patients followed for an average of 10 years, Dr. Wayne Gulliver said in presenting preliminary results of the ongoing study at the annual congress of the European Academy of Dermatology and Venereology.

The issue of a possible elevated risk of lymphoma in psoriasis patients has been controversial. Findings have been inconsistent. Some studies have reported a significantly increased risk. Among these, notably, was a population-based cohort study of more than 153,000 psoriasis patients and close to 800,000 controls in the U.K. General Practice Research Database. Investigators found an age- and sex-adjusted 35% increased risk of lymphoma in the group with psoriasis (J. Invest. Dermatol. 2006;126:2194-201).

However, lymphoma is an uncommon disease and a 35% increased risk is, from an epidemiologic perspective, only modest. Some studies have not found a significant association between psoriasis and lymphoma. The Canadian maritime study can be added to their ranks, according to Dr. Gulliver, professor of medicine and chairman of the division of dermatology at Memorial University of Newfoundland, St. John’s.

He matched records from a comprehensive research database of psoriasis patients in Newfoundland and Labrador for 1989-2010 with Canadian national and provincial cancer statistics. The purpose of the study was straightforward: "Our patients want to know if their psoriasis affects their risk of cancer, especially with the treatments we’re offering them these days," Dr. Gulliver said.

There were 232 cancer cases in 3,289 psoriasis patients, for a cumulative incidence rate of 588/100,000 population with psoriasis. Although the psoriasis population was divided nearly equally between men and women, 145 men developed cancer compared with 87 women.

Cancer rates were similar regardless of whether patients had mild psoriasis – meaning they received no systemic therapies – or moderate to severe psoriasis.

The cumulative incidence rate of breast cancer among psoriasis patients was 52/100,000 patients with mild psoriasis and 64/100,000 with moderate to severe disease compared with 96/100,000 in the general Canadian population and 84/100,000 among residents of Newfoundland and Labrador. The prostate cancer rate was 103/100,000 patients with mild psoriasis and 75/100,000 with moderate to severe psoriasis as opposed to 121/100,000 nationwide and 129/100,000 men in the general population of the two maritime provinces. The cumulative incidence rate for colorectal cancer followed the same pattern: lower in the psoriasis patients than in the general population.

Nonmelanoma skin cancer rates were relatively high: 142/100,000 patients with mild psoriasis and 122/100,000 with moderate to severe disease. That’s consistent with findings from other studies. It comes as no surprise given the common use of UV therapy and sunlight exposure in psoriasis patients.

Dr. Gulliver noted the relatively small number of cancers to date is a significant study limitation. But that number will grow as the psoriasis patients age; plus, more psoriasis patients are being added to the provincial database. He added that the database provides fertile ground for planned future studies. He said he plans soon to compare cancer rates in psoriasis patients on immunosuppressive therapy with biologic agents or cyclosporine to rates in patients on other agents.

One audience member observed that it seems more than coincidental that increased rates of breast, prostate, and colorectal cancers in the general population have previously been linked to low vitamin D levels. Perhaps the same factor that drives the increase in nonmelanoma skin cancer in psoriasis patients – that is, UV exposure – is responsible for their lower risks of those three common internal malignancies through a mechanism involving enhanced serum vitamin D levels, he speculated.

Dr. Gulliver called that a fascinating hypothesis and one he is now eager to investigate, since he has access to blood samples for the study population.

The study was free of commercial involvement, and the presenter reported having no relevant financial conflicts.

LOS ANGELES – Hospital-acquired bleeding in patients admitted for atrial fibrillation is a very costly event, as demonstrated in the first large national study to put a price tag on this occurrence.

This retrospective observational study was undertaken because even though the clinical and economic toll of stroke in patients with atrial fibrillation (AF) has been well characterized, only scanty information has previously been available on the impact of inpatient bleeding in patients with this most common of arrhythmias, Dr. Alpesh N. Amin explained at the annual scientific sessions of the American Heart Association.

He and his coinvestigators searched the Premier Research Database, which contains patient encounter data from more than 500 U.S. hospitals, in order to identify 143,415 adults hospitalized with a primary diagnosis of nonvalvular AF with no bleeding upon admission during 2008-2011.

A bleeding event requiring administration of blood products occurred in 2.1% of patients. Their unadjusted mean length of stay was 8.8 days, compared with 3.4 days in AF patients without bleeding. After adjustment for comorbid conditions, hospital characteristics, patient demographics, and administration of anticoagulants or antiplatelet agents at any time during the hospitalization, the mean length of stay was 6.7 days in AF patients with bleeding, compared with 3.3 days in those without, according to Dr. Amin, professor and chair of the department of medicine and executive director of the hospitalist program at the University of California, Irvine.

The adjusted mean total cost of the hospital stay in AF patients with hospital-acquired bleeding was $16,621, compared with $6,997 in those without bleeding.

In this study population comprising more than 143,000 patients with AF, bleeding during a hospital stay added roughly $30 million in costs and 10,397 extra days in the hospital, compared with no bleeding.

This study was sponsored by Bristol-Myers Squibb and Pfizer. Dr. Amin reported receiving a research grant from Pfizer.

LOS ANGELES – Hospital-acquired bleeding in patients admitted for atrial fibrillation is a very costly event, as demonstrated in the first large national study to put a price tag on this occurrence.

This retrospective observational study was undertaken because even though the clinical and economic toll of stroke in patients with atrial fibrillation (AF) has been well characterized, only scanty information has previously been available on the impact of inpatient bleeding in patients with this most common of arrhythmias, Dr. Alpesh N. Amin explained at the annual scientific sessions of the American Heart Association.

He and his coinvestigators searched the Premier Research Database, which contains patient encounter data from more than 500 U.S. hospitals, in order to identify 143,415 adults hospitalized with a primary diagnosis of nonvalvular AF with no bleeding upon admission during 2008-2011.

A bleeding event requiring administration of blood products occurred in 2.1% of patients. Their unadjusted mean length of stay was 8.8 days, compared with 3.4 days in AF patients without bleeding. After adjustment for comorbid conditions, hospital characteristics, patient demographics, and administration of anticoagulants or antiplatelet agents at any time during the hospitalization, the mean length of stay was 6.7 days in AF patients with bleeding, compared with 3.3 days in those without, according to Dr. Amin, professor and chair of the department of medicine and executive director of the hospitalist program at the University of California, Irvine.

The adjusted mean total cost of the hospital stay in AF patients with hospital-acquired bleeding was $16,621, compared with $6,997 in those without bleeding.

In this study population comprising more than 143,000 patients with AF, bleeding during a hospital stay added roughly $30 million in costs and 10,397 extra days in the hospital, compared with no bleeding.

This study was sponsored by Bristol-Myers Squibb and Pfizer. Dr. Amin reported receiving a research grant from Pfizer.

LOS ANGELES – Hospital-acquired bleeding in patients admitted for atrial fibrillation is a very costly event, as demonstrated in the first large national study to put a price tag on this occurrence.

This retrospective observational study was undertaken because even though the clinical and economic toll of stroke in patients with atrial fibrillation (AF) has been well characterized, only scanty information has previously been available on the impact of inpatient bleeding in patients with this most common of arrhythmias, Dr. Alpesh N. Amin explained at the annual scientific sessions of the American Heart Association.

He and his coinvestigators searched the Premier Research Database, which contains patient encounter data from more than 500 U.S. hospitals, in order to identify 143,415 adults hospitalized with a primary diagnosis of nonvalvular AF with no bleeding upon admission during 2008-2011.

A bleeding event requiring administration of blood products occurred in 2.1% of patients. Their unadjusted mean length of stay was 8.8 days, compared with 3.4 days in AF patients without bleeding. After adjustment for comorbid conditions, hospital characteristics, patient demographics, and administration of anticoagulants or antiplatelet agents at any time during the hospitalization, the mean length of stay was 6.7 days in AF patients with bleeding, compared with 3.3 days in those without, according to Dr. Amin, professor and chair of the department of medicine and executive director of the hospitalist program at the University of California, Irvine.

The adjusted mean total cost of the hospital stay in AF patients with hospital-acquired bleeding was $16,621, compared with $6,997 in those without bleeding.

In this study population comprising more than 143,000 patients with AF, bleeding during a hospital stay added roughly $30 million in costs and 10,397 extra days in the hospital, compared with no bleeding.

This study was sponsored by Bristol-Myers Squibb and Pfizer. Dr. Amin reported receiving a research grant from Pfizer.

LOS ANGELES – A once-daily, fixed-dose combination of four cardiovascular drugs – a polypill – boosted patient adherence by 33% while meaningfully reducing both systolic blood pressure and LDL cholesterol compared with usual care in the large international UMPIRE trial.

UMPIRE (Use of a Multidrug Pill in Reducing Cardiovascular Events) was designed to test the hypothesis that decreasing the cost and complexity of guideline-indicated medications for secondary cardiovascular prevention would improve treatment adherence and outcomes in patients with established atherosclerotic cardiovascular disease or in those at high risk for it.

And UMPIRE was a resounding success, according to Dr. Simon Thom, professor of cardiovascular medicine and pharmacology at Imperial College, London. He presented the results at the annual scientific sessions of the American Heart Association.

The study comprised 2,004 randomized patients in India, Dublin, London, and Utrecht (the Netherlands): 88% had known atherosclerotic cardiovascular disease at baseline; 29% had diabetes. Participants were randomized to the polypill – composed of 75 mg aspirin, 50 mg simvastatin, 10 mg lisinopril, and either 50 mg atenolol or 12.5 mg hydrochlorothiazide, depending upon physician preference – or to usual care, which included individual prescriptions for the same four medications. The polypill was free, while usual care was paid for in the customary local manner.

After a median 15 months of follow-up, treatment adherence was 86% in the polypill arm, compared with 65% with usual care, a relative 33% difference. Systolic blood pressure averaged 129.2 mm Hg in the polypill group, 2.6 mm Hg lower than with usual care. Mean LDL cholesterol was 84.3 mg/dL in the polypill group and 88.6 mg/dL with usual care. Diastolic blood pressure was 72.8 mm Hg with the polypill, compared with 75.2 mm Hg in the usual care group.

All of these differences were statistically significant and clinically meaningful when extrapolated to the rapidly growing global burden of cardiovascular disease. Moreover, quality of life as self-measured on a visual analog scale was significantly better in patients on the fixed-dose combination, Dr. Thom reported.

There were, however, no significant differences between the two study arms in HDL cholesterol, triglycerides, or cardiovascular event rates.

Of note, 61% of UMPIRE subjects were already on all four individual study medications at baseline. That’s an unusually high proportion in the low- and middle-income countries where the polypill will see greatest future use, and it means the UMPIRE results almost certainly underestimate the true benefits to be expected with use of the polypill in clinical practice, he continued.

Side effects were the same in both treatment arms.

Discussant Dr. Andrew M. Tonkin declared UMPIRE to be "an important trial – and the results should be taken on board not only by clinicians, but should really inform government policies and strategies."

Although there is enthusiasm in some quarters for broad use of the polypill for primary prevention – a sort of let’s-put-it-in-the-drinking-water strategy – UMPIRE was the first polypill randomized trial conducted in patients with established cardiovascular disease, and one of very few to date to run longer than about 3 months.

"I believe that UMPIRE firmly establishes the case for using the polypill in those people with manifest atherosclerotic cardiovascular disease," said Dr. Tonkin.

It’s noteworthy that patients with poor baseline adherence to the study medications were 3.4-fold more likely to benefit from use of the polypill. That’s an important finding because the polypill is expected to see its greatest future use in India, China, the Philippines, and other parts of the world where vast numbers of patients with cardiovascular disease now receive little or nothing in the way of pharmacologic secondary prevention, said Dr. Tonkin, professor of preventive medicine and head of the cardiovascular research unit at Monash Hospital in Melbourne.

Moving forward, he added, the responsibility for developing the polypill cannot rest solely with the pharmaceutical industry.

"This is a very low-margin venture using low-cost generic formulations. Major pharma doesn’t want to get interested in this," said Dr. Tonkin.

Both the World Health Organization and the European Commission are publicly on board for the polypill, he noted.

The WHO and Wellcome Trust stated in a 2002 report that demonstration of bioequivalence and improved adherence as reflected in improvements in LDL and systolic blood pressure, as seen in UMPIRE, should be sufficient for regulatory approval of the polypill.

"That, I think, will not carry water in these days, unfortunately. But a meta-analysis of clinical end point data from the various trials is planned. And there are ongoing and planned future phase III trials," Dr. Tonkin said.

While most of the clinical trials, past and present, have taken place in low-income countries, the polypill is also under study in populations in the United States, Canada, Australia, and other relatively well-off nations, he pointed out.

UMPIRE was funded by the European Commission. Dr. Thom and Dr. Tonkin reported having no financial conflicts.

LOS ANGELES – A once-daily, fixed-dose combination of four cardiovascular drugs – a polypill – boosted patient adherence by 33% while meaningfully reducing both systolic blood pressure and LDL cholesterol compared with usual care in the large international UMPIRE trial.

UMPIRE (Use of a Multidrug Pill in Reducing Cardiovascular Events) was designed to test the hypothesis that decreasing the cost and complexity of guideline-indicated medications for secondary cardiovascular prevention would improve treatment adherence and outcomes in patients with established atherosclerotic cardiovascular disease or in those at high risk for it.

And UMPIRE was a resounding success, according to Dr. Simon Thom, professor of cardiovascular medicine and pharmacology at Imperial College, London. He presented the results at the annual scientific sessions of the American Heart Association.

The study comprised 2,004 randomized patients in India, Dublin, London, and Utrecht (the Netherlands): 88% had known atherosclerotic cardiovascular disease at baseline; 29% had diabetes. Participants were randomized to the polypill – composed of 75 mg aspirin, 50 mg simvastatin, 10 mg lisinopril, and either 50 mg atenolol or 12.5 mg hydrochlorothiazide, depending upon physician preference – or to usual care, which included individual prescriptions for the same four medications. The polypill was free, while usual care was paid for in the customary local manner.

After a median 15 months of follow-up, treatment adherence was 86% in the polypill arm, compared with 65% with usual care, a relative 33% difference. Systolic blood pressure averaged 129.2 mm Hg in the polypill group, 2.6 mm Hg lower than with usual care. Mean LDL cholesterol was 84.3 mg/dL in the polypill group and 88.6 mg/dL with usual care. Diastolic blood pressure was 72.8 mm Hg with the polypill, compared with 75.2 mm Hg in the usual care group.

All of these differences were statistically significant and clinically meaningful when extrapolated to the rapidly growing global burden of cardiovascular disease. Moreover, quality of life as self-measured on a visual analog scale was significantly better in patients on the fixed-dose combination, Dr. Thom reported.

There were, however, no significant differences between the two study arms in HDL cholesterol, triglycerides, or cardiovascular event rates.

Of note, 61% of UMPIRE subjects were already on all four individual study medications at baseline. That’s an unusually high proportion in the low- and middle-income countries where the polypill will see greatest future use, and it means the UMPIRE results almost certainly underestimate the true benefits to be expected with use of the polypill in clinical practice, he continued.

Side effects were the same in both treatment arms.

Discussant Dr. Andrew M. Tonkin declared UMPIRE to be "an important trial – and the results should be taken on board not only by clinicians, but should really inform government policies and strategies."

Although there is enthusiasm in some quarters for broad use of the polypill for primary prevention – a sort of let’s-put-it-in-the-drinking-water strategy – UMPIRE was the first polypill randomized trial conducted in patients with established cardiovascular disease, and one of very few to date to run longer than about 3 months.

"I believe that UMPIRE firmly establishes the case for using the polypill in those people with manifest atherosclerotic cardiovascular disease," said Dr. Tonkin.

It’s noteworthy that patients with poor baseline adherence to the study medications were 3.4-fold more likely to benefit from use of the polypill. That’s an important finding because the polypill is expected to see its greatest future use in India, China, the Philippines, and other parts of the world where vast numbers of patients with cardiovascular disease now receive little or nothing in the way of pharmacologic secondary prevention, said Dr. Tonkin, professor of preventive medicine and head of the cardiovascular research unit at Monash Hospital in Melbourne.

Moving forward, he added, the responsibility for developing the polypill cannot rest solely with the pharmaceutical industry.

"This is a very low-margin venture using low-cost generic formulations. Major pharma doesn’t want to get interested in this," said Dr. Tonkin.

Both the World Health Organization and the European Commission are publicly on board for the polypill, he noted.

The WHO and Wellcome Trust stated in a 2002 report that demonstration of bioequivalence and improved adherence as reflected in improvements in LDL and systolic blood pressure, as seen in UMPIRE, should be sufficient for regulatory approval of the polypill.

"That, I think, will not carry water in these days, unfortunately. But a meta-analysis of clinical end point data from the various trials is planned. And there are ongoing and planned future phase III trials," Dr. Tonkin said.

While most of the clinical trials, past and present, have taken place in low-income countries, the polypill is also under study in populations in the United States, Canada, Australia, and other relatively well-off nations, he pointed out.

UMPIRE was funded by the European Commission. Dr. Thom and Dr. Tonkin reported having no financial conflicts.

LOS ANGELES – A once-daily, fixed-dose combination of four cardiovascular drugs – a polypill – boosted patient adherence by 33% while meaningfully reducing both systolic blood pressure and LDL cholesterol compared with usual care in the large international UMPIRE trial.

UMPIRE (Use of a Multidrug Pill in Reducing Cardiovascular Events) was designed to test the hypothesis that decreasing the cost and complexity of guideline-indicated medications for secondary cardiovascular prevention would improve treatment adherence and outcomes in patients with established atherosclerotic cardiovascular disease or in those at high risk for it.

And UMPIRE was a resounding success, according to Dr. Simon Thom, professor of cardiovascular medicine and pharmacology at Imperial College, London. He presented the results at the annual scientific sessions of the American Heart Association.

The study comprised 2,004 randomized patients in India, Dublin, London, and Utrecht (the Netherlands): 88% had known atherosclerotic cardiovascular disease at baseline; 29% had diabetes. Participants were randomized to the polypill – composed of 75 mg aspirin, 50 mg simvastatin, 10 mg lisinopril, and either 50 mg atenolol or 12.5 mg hydrochlorothiazide, depending upon physician preference – or to usual care, which included individual prescriptions for the same four medications. The polypill was free, while usual care was paid for in the customary local manner.

After a median 15 months of follow-up, treatment adherence was 86% in the polypill arm, compared with 65% with usual care, a relative 33% difference. Systolic blood pressure averaged 129.2 mm Hg in the polypill group, 2.6 mm Hg lower than with usual care. Mean LDL cholesterol was 84.3 mg/dL in the polypill group and 88.6 mg/dL with usual care. Diastolic blood pressure was 72.8 mm Hg with the polypill, compared with 75.2 mm Hg in the usual care group.

All of these differences were statistically significant and clinically meaningful when extrapolated to the rapidly growing global burden of cardiovascular disease. Moreover, quality of life as self-measured on a visual analog scale was significantly better in patients on the fixed-dose combination, Dr. Thom reported.

There were, however, no significant differences between the two study arms in HDL cholesterol, triglycerides, or cardiovascular event rates.

Of note, 61% of UMPIRE subjects were already on all four individual study medications at baseline. That’s an unusually high proportion in the low- and middle-income countries where the polypill will see greatest future use, and it means the UMPIRE results almost certainly underestimate the true benefits to be expected with use of the polypill in clinical practice, he continued.

Side effects were the same in both treatment arms.

Discussant Dr. Andrew M. Tonkin declared UMPIRE to be "an important trial – and the results should be taken on board not only by clinicians, but should really inform government policies and strategies."

Although there is enthusiasm in some quarters for broad use of the polypill for primary prevention – a sort of let’s-put-it-in-the-drinking-water strategy – UMPIRE was the first polypill randomized trial conducted in patients with established cardiovascular disease, and one of very few to date to run longer than about 3 months.

"I believe that UMPIRE firmly establishes the case for using the polypill in those people with manifest atherosclerotic cardiovascular disease," said Dr. Tonkin.

It’s noteworthy that patients with poor baseline adherence to the study medications were 3.4-fold more likely to benefit from use of the polypill. That’s an important finding because the polypill is expected to see its greatest future use in India, China, the Philippines, and other parts of the world where vast numbers of patients with cardiovascular disease now receive little or nothing in the way of pharmacologic secondary prevention, said Dr. Tonkin, professor of preventive medicine and head of the cardiovascular research unit at Monash Hospital in Melbourne.

Moving forward, he added, the responsibility for developing the polypill cannot rest solely with the pharmaceutical industry.

"This is a very low-margin venture using low-cost generic formulations. Major pharma doesn’t want to get interested in this," said Dr. Tonkin.

Both the World Health Organization and the European Commission are publicly on board for the polypill, he noted.

The WHO and Wellcome Trust stated in a 2002 report that demonstration of bioequivalence and improved adherence as reflected in improvements in LDL and systolic blood pressure, as seen in UMPIRE, should be sufficient for regulatory approval of the polypill.

"That, I think, will not carry water in these days, unfortunately. But a meta-analysis of clinical end point data from the various trials is planned. And there are ongoing and planned future phase III trials," Dr. Tonkin said.

While most of the clinical trials, past and present, have taken place in low-income countries, the polypill is also under study in populations in the United States, Canada, Australia, and other relatively well-off nations, he pointed out.

UMPIRE was funded by the European Commission. Dr. Thom and Dr. Tonkin reported having no financial conflicts.

PRAGUE – Recent evidence dictates the need to reassess the roles of doxycycline and azithromycin in treating Chlamydia trachomatis nongonococcal urethritis, according to Dr. Michel Janier.

Current first-line therapy for nongonococcal urethritis (NGU), as recommended by the Centers for Disease Control and Prevention and other major groups, features a choice: a single 1-g dose of azithromycin, or doxycycline at 100 mg b.i.d. for 7 days. Single-dose azithromycin is a popular option, given its convenience and likely better adherence.

CDC/Dr. E. Arum; Dr. N. Jacobs

But a couple of important head-to-head comparative trials published recently are making waves in the infectious disease world. Doxycycline proved significantly more effective than azithromycin in clearing chlamydial NGU in one study and had a markedly lower C. trachomatis persistence rate 45 days post treatment in the other, said Dr. Janier, head of dermatology at Saint Joseph Hospital in Paris and the French representative to the International Union Against Sexually Transmitted Infections–Europe.

One study was a phase IIb randomized, double-blind trial involving 305 men with NGU at sexually transmitted disease clinics in four U.S. cities. They were assigned to guideline-recommended treatment with either azithromycin or doxycycline alone or with a single 2-g dose of tinidazole, an antitrichomonal agent, in order to test the hypothesis that adding the second agent would boost cure rates. As it turned out, it did not.

Among the 43% of men with C. trachomatis NGU, the chlamydial clearance rate was 94.8% in the doxycycline arm compared with 77.4% with azithromycin.

While doxycycline outperformed azithromycin in men with C. trachomatis NGU, the converse was true among the 31% of participants with Mycoplasma genitalium NGU. The clearance rate was 30.8% in the doxycycline arm compared with 66.7% in the azithromycin arm (Clin. Infect. Dis. 2011;52:163-70).

The same group of investigators recently analyzed data on post-treatment persistence of NGU in a study involving 293 heterosexual men treated for NGU at STD clinics. Among the 129 men with C. trachomatis NGU, persistent C. trachomatis infection was detected via nucleic acid amplification testing 4 weeks post treatment in 23% of those who received azithromycin compared with just 5% treated with doxycycline (J. Infect. Dis. 2012;206:357-65).

The explanation for the observed higher failure rate with azithromycin compared with doxycycline in treating chlamydial NGU is probably twofold: homotypic resistance of the organism to a single dose of a bacteriostatic antibiotic, coupled with heterotopic resistance stemming from a persistent subpopulation of cells having a reduced growth rate within the larger pathogen load, Dr. Janier said.

He added that while it’s important not to overreact to a couple of studies carried out by a single group, there is intense interest on the part of many infectious disease experts in taking a closer look at the possibility that azithromycin may need to be dethroned as first-line therapy.

The dermatologist also highlighted another recent study that bears on the treatment of uncomplicated C. trachomatis NGU. The double-blind, randomized, double-dummy multicenter trial included 323 men and nonpregnant women with urogenital chlamydia. They were randomized to 7 days of once-daily delayed-release doxycycline (Doryx) at 200 mg or to 100 mg b.i.d. of standard-release doxycycline (Vibramycin).

The primary outcome, microbial cure by nucleic acid amplification testing on day 28, occurred in 95.5% of the delayed-release doxycycline group and a virtually identical 95.2% on Vibramycin. However, the delayed-release formulation was significantly better tolerated, with a 13% nausea rate compared with 21% in the Vibramycin group. Vomiting occurred in 8% of patients on delayed-release doxycycline, a significantly lower rate than the 12% with Vibramycin.

The investigators concluded that delayed-release doxycycline, with its once-daily dosing and better tolerability, could improve treatment adherence (Clin. Infect. Dis. 2012; 55: 82-8).

Dr. Janier reported having no relevant financial disclosures.

PRAGUE – Recent evidence dictates the need to reassess the roles of doxycycline and azithromycin in treating Chlamydia trachomatis nongonococcal urethritis, according to Dr. Michel Janier.

Current first-line therapy for nongonococcal urethritis (NGU), as recommended by the Centers for Disease Control and Prevention and other major groups, features a choice: a single 1-g dose of azithromycin, or doxycycline at 100 mg b.i.d. for 7 days. Single-dose azithromycin is a popular option, given its convenience and likely better adherence.

CDC/Dr. E. Arum; Dr. N. Jacobs

But a couple of important head-to-head comparative trials published recently are making waves in the infectious disease world. Doxycycline proved significantly more effective than azithromycin in clearing chlamydial NGU in one study and had a markedly lower C. trachomatis persistence rate 45 days post treatment in the other, said Dr. Janier, head of dermatology at Saint Joseph Hospital in Paris and the French representative to the International Union Against Sexually Transmitted Infections–Europe.

One study was a phase IIb randomized, double-blind trial involving 305 men with NGU at sexually transmitted disease clinics in four U.S. cities. They were assigned to guideline-recommended treatment with either azithromycin or doxycycline alone or with a single 2-g dose of tinidazole, an antitrichomonal agent, in order to test the hypothesis that adding the second agent would boost cure rates. As it turned out, it did not.

Among the 43% of men with C. trachomatis NGU, the chlamydial clearance rate was 94.8% in the doxycycline arm compared with 77.4% with azithromycin.

While doxycycline outperformed azithromycin in men with C. trachomatis NGU, the converse was true among the 31% of participants with Mycoplasma genitalium NGU. The clearance rate was 30.8% in the doxycycline arm compared with 66.7% in the azithromycin arm (Clin. Infect. Dis. 2011;52:163-70).

The same group of investigators recently analyzed data on post-treatment persistence of NGU in a study involving 293 heterosexual men treated for NGU at STD clinics. Among the 129 men with C. trachomatis NGU, persistent C. trachomatis infection was detected via nucleic acid amplification testing 4 weeks post treatment in 23% of those who received azithromycin compared with just 5% treated with doxycycline (J. Infect. Dis. 2012;206:357-65).

The explanation for the observed higher failure rate with azithromycin compared with doxycycline in treating chlamydial NGU is probably twofold: homotypic resistance of the organism to a single dose of a bacteriostatic antibiotic, coupled with heterotopic resistance stemming from a persistent subpopulation of cells having a reduced growth rate within the larger pathogen load, Dr. Janier said.

He added that while it’s important not to overreact to a couple of studies carried out by a single group, there is intense interest on the part of many infectious disease experts in taking a closer look at the possibility that azithromycin may need to be dethroned as first-line therapy.

The dermatologist also highlighted another recent study that bears on the treatment of uncomplicated C. trachomatis NGU. The double-blind, randomized, double-dummy multicenter trial included 323 men and nonpregnant women with urogenital chlamydia. They were randomized to 7 days of once-daily delayed-release doxycycline (Doryx) at 200 mg or to 100 mg b.i.d. of standard-release doxycycline (Vibramycin).

The primary outcome, microbial cure by nucleic acid amplification testing on day 28, occurred in 95.5% of the delayed-release doxycycline group and a virtually identical 95.2% on Vibramycin. However, the delayed-release formulation was significantly better tolerated, with a 13% nausea rate compared with 21% in the Vibramycin group. Vomiting occurred in 8% of patients on delayed-release doxycycline, a significantly lower rate than the 12% with Vibramycin.

The investigators concluded that delayed-release doxycycline, with its once-daily dosing and better tolerability, could improve treatment adherence (Clin. Infect. Dis. 2012; 55: 82-8).

Dr. Janier reported having no relevant financial disclosures.

PRAGUE – Recent evidence dictates the need to reassess the roles of doxycycline and azithromycin in treating Chlamydia trachomatis nongonococcal urethritis, according to Dr. Michel Janier.

Current first-line therapy for nongonococcal urethritis (NGU), as recommended by the Centers for Disease Control and Prevention and other major groups, features a choice: a single 1-g dose of azithromycin, or doxycycline at 100 mg b.i.d. for 7 days. Single-dose azithromycin is a popular option, given its convenience and likely better adherence.

CDC/Dr. E. Arum; Dr. N. Jacobs

But a couple of important head-to-head comparative trials published recently are making waves in the infectious disease world. Doxycycline proved significantly more effective than azithromycin in clearing chlamydial NGU in one study and had a markedly lower C. trachomatis persistence rate 45 days post treatment in the other, said Dr. Janier, head of dermatology at Saint Joseph Hospital in Paris and the French representative to the International Union Against Sexually Transmitted Infections–Europe.

One study was a phase IIb randomized, double-blind trial involving 305 men with NGU at sexually transmitted disease clinics in four U.S. cities. They were assigned to guideline-recommended treatment with either azithromycin or doxycycline alone or with a single 2-g dose of tinidazole, an antitrichomonal agent, in order to test the hypothesis that adding the second agent would boost cure rates. As it turned out, it did not.

Among the 43% of men with C. trachomatis NGU, the chlamydial clearance rate was 94.8% in the doxycycline arm compared with 77.4% with azithromycin.

While doxycycline outperformed azithromycin in men with C. trachomatis NGU, the converse was true among the 31% of participants with Mycoplasma genitalium NGU. The clearance rate was 30.8% in the doxycycline arm compared with 66.7% in the azithromycin arm (Clin. Infect. Dis. 2011;52:163-70).

The same group of investigators recently analyzed data on post-treatment persistence of NGU in a study involving 293 heterosexual men treated for NGU at STD clinics. Among the 129 men with C. trachomatis NGU, persistent C. trachomatis infection was detected via nucleic acid amplification testing 4 weeks post treatment in 23% of those who received azithromycin compared with just 5% treated with doxycycline (J. Infect. Dis. 2012;206:357-65).

The explanation for the observed higher failure rate with azithromycin compared with doxycycline in treating chlamydial NGU is probably twofold: homotypic resistance of the organism to a single dose of a bacteriostatic antibiotic, coupled with heterotopic resistance stemming from a persistent subpopulation of cells having a reduced growth rate within the larger pathogen load, Dr. Janier said.

He added that while it’s important not to overreact to a couple of studies carried out by a single group, there is intense interest on the part of many infectious disease experts in taking a closer look at the possibility that azithromycin may need to be dethroned as first-line therapy.

The dermatologist also highlighted another recent study that bears on the treatment of uncomplicated C. trachomatis NGU. The double-blind, randomized, double-dummy multicenter trial included 323 men and nonpregnant women with urogenital chlamydia. They were randomized to 7 days of once-daily delayed-release doxycycline (Doryx) at 200 mg or to 100 mg b.i.d. of standard-release doxycycline (Vibramycin).

The primary outcome, microbial cure by nucleic acid amplification testing on day 28, occurred in 95.5% of the delayed-release doxycycline group and a virtually identical 95.2% on Vibramycin. However, the delayed-release formulation was significantly better tolerated, with a 13% nausea rate compared with 21% in the Vibramycin group. Vomiting occurred in 8% of patients on delayed-release doxycycline, a significantly lower rate than the 12% with Vibramycin.

The investigators concluded that delayed-release doxycycline, with its once-daily dosing and better tolerability, could improve treatment adherence (Clin. Infect. Dis. 2012; 55: 82-8).

Dr. Janier reported having no relevant financial disclosures.

LOS ANGELES – Chronic heart failure patients who ate a special superhigh-flavonol dark chocolate bar daily experienced favorable changes consistent with decreased vascular resistance and diminished left ventricular afterload in a randomized, double-blind, crossover pilot study.

"It should be emphasized that these patients were already on maximal tolerated guideline-indicated therapy. In terms of medical interventions, there weren’t many more things we could do. So I think that in addition to looking at new drugs, we need to look at evidence-based new diets to see if they can reduce morbidity and mortality in heart failure," Dr. Roger Corder said in presenting the chocolate study results at the annual scientific sessions of the American Heart Association.

The likely mechanism of benefit in heart failure patients involves a dark chocolate–induced reduction in endothelial dysfunction.

"Prior studies show consumption of cocoa flavonols in daily doses of 750 mg or more improve endothelial function in patients with coronary artery disease, in healthy subjects, and in diabetics," noted Dr. Corder of Queen Mary University of London.

The study involved 32 patients with stable heart failure on maximal medical therapy, all of whom had a history of ischemic heart disease. They were randomized to daily consumption of a 50-g bar of high-flavonol chocolate or a low-flavonol chocolate bar for 4 weeks, then crossed over to daily consumption of the other bar for another 4 weeks.

The test product contained 1,094 mg of flavonols per bar, while the low-flavonol comparator contained 95 mg. The high-flavonol chocolate bar was a custom-made product whose flavonol content far exceeds anything on the market. Dr. Corder and coinvestigators tested 50 brands of commercially available dark chocolate bars averaging 76% cocoa solids and determined their average flavonol content was 312 mg/50 g.

The study end points were change in diastolic blood pressure and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels after 4 weeks of eating each type of chocolate bar.

Twenty-four patients completed the study. Mean NT-proBNP dropped by an average of 39% from a baseline of 200 pmol/L after 4 weeks of eating the high-flavonol chocolate.

"Given that other trials of medications, including angiotensin receptor blockers, have shown a 30% reduction in NT-proBNP is associated with improved clinical outcomes, this looks to us like something of interest to pursue further with additional clinical studies. It’s worth noting that 12 of the 24 patients had a drop in NT-proBNP of 30% or more," Dr. Corder said.

From a baseline blood pressure of 126/71 mm Hg, diastolic pressure fell by 5 mm Hg in conjunction with consumption of the high-flavonol bar. Systolic pressure did not change significantly. Maintenance of systolic blood pressure with a reduction in diastolic pressure implies an increase in cardiac output – "and that would really be the optimum thing to have happened," he continued.

The low-flavonol chocolate bar did not produce changes in blood pressure or NT-proBNP.

A couple of down sides with the experimental high-flavonol chocolate bar emerged during the study. One was taste. Three of the eight study dropouts quit because they found the product’s taste unacceptable, while the others left for reasons unrelated to the study.

"We had an issue with taste. Even the patients who finished the study didn’t like the taste. There may be other countries where dark chocolate is popular, but the East of London would rather have their sweet milk chocolate than dark chocolate," according to Dr. Corder.

Weight gain is another concern. Both chocolate bars contained about 19 g of fat, including 12 g of saturated fat, per 50-g serving, with about 260 calories. From a baseline body weight of 85.7 kg, participants gained roughly 0.3 kg over the course of 4 weeks.

"In terms of long-term therapy, it may not be suitable to take dark chocolate on a daily basis at this level," he said.

However, food scientists involved in the study are tweaking the recipe to improve the taste of the superhigh-flavonol bar. There is also the option of extracting the flavonols and placing them in some other nutraceutical food product.

The study was funded by Swiss chocolate giant Barry Callebaut. Dr. Corder reported receiving a significant research grant from the company.

LOS ANGELES – Chronic heart failure patients who ate a special superhigh-flavonol dark chocolate bar daily experienced favorable changes consistent with decreased vascular resistance and diminished left ventricular afterload in a randomized, double-blind, crossover pilot study.

"It should be emphasized that these patients were already on maximal tolerated guideline-indicated therapy. In terms of medical interventions, there weren’t many more things we could do. So I think that in addition to looking at new drugs, we need to look at evidence-based new diets to see if they can reduce morbidity and mortality in heart failure," Dr. Roger Corder said in presenting the chocolate study results at the annual scientific sessions of the American Heart Association.

The likely mechanism of benefit in heart failure patients involves a dark chocolate–induced reduction in endothelial dysfunction.

"Prior studies show consumption of cocoa flavonols in daily doses of 750 mg or more improve endothelial function in patients with coronary artery disease, in healthy subjects, and in diabetics," noted Dr. Corder of Queen Mary University of London.

The study involved 32 patients with stable heart failure on maximal medical therapy, all of whom had a history of ischemic heart disease. They were randomized to daily consumption of a 50-g bar of high-flavonol chocolate or a low-flavonol chocolate bar for 4 weeks, then crossed over to daily consumption of the other bar for another 4 weeks.

The test product contained 1,094 mg of flavonols per bar, while the low-flavonol comparator contained 95 mg. The high-flavonol chocolate bar was a custom-made product whose flavonol content far exceeds anything on the market. Dr. Corder and coinvestigators tested 50 brands of commercially available dark chocolate bars averaging 76% cocoa solids and determined their average flavonol content was 312 mg/50 g.

The study end points were change in diastolic blood pressure and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels after 4 weeks of eating each type of chocolate bar.

Twenty-four patients completed the study. Mean NT-proBNP dropped by an average of 39% from a baseline of 200 pmol/L after 4 weeks of eating the high-flavonol chocolate.

"Given that other trials of medications, including angiotensin receptor blockers, have shown a 30% reduction in NT-proBNP is associated with improved clinical outcomes, this looks to us like something of interest to pursue further with additional clinical studies. It’s worth noting that 12 of the 24 patients had a drop in NT-proBNP of 30% or more," Dr. Corder said.

From a baseline blood pressure of 126/71 mm Hg, diastolic pressure fell by 5 mm Hg in conjunction with consumption of the high-flavonol bar. Systolic pressure did not change significantly. Maintenance of systolic blood pressure with a reduction in diastolic pressure implies an increase in cardiac output – "and that would really be the optimum thing to have happened," he continued.

The low-flavonol chocolate bar did not produce changes in blood pressure or NT-proBNP.

A couple of down sides with the experimental high-flavonol chocolate bar emerged during the study. One was taste. Three of the eight study dropouts quit because they found the product’s taste unacceptable, while the others left for reasons unrelated to the study.

"We had an issue with taste. Even the patients who finished the study didn’t like the taste. There may be other countries where dark chocolate is popular, but the East of London would rather have their sweet milk chocolate than dark chocolate," according to Dr. Corder.

Weight gain is another concern. Both chocolate bars contained about 19 g of fat, including 12 g of saturated fat, per 50-g serving, with about 260 calories. From a baseline body weight of 85.7 kg, participants gained roughly 0.3 kg over the course of 4 weeks.

"In terms of long-term therapy, it may not be suitable to take dark chocolate on a daily basis at this level," he said.

However, food scientists involved in the study are tweaking the recipe to improve the taste of the superhigh-flavonol bar. There is also the option of extracting the flavonols and placing them in some other nutraceutical food product.

The study was funded by Swiss chocolate giant Barry Callebaut. Dr. Corder reported receiving a significant research grant from the company.

LOS ANGELES – Chronic heart failure patients who ate a special superhigh-flavonol dark chocolate bar daily experienced favorable changes consistent with decreased vascular resistance and diminished left ventricular afterload in a randomized, double-blind, crossover pilot study.

"It should be emphasized that these patients were already on maximal tolerated guideline-indicated therapy. In terms of medical interventions, there weren’t many more things we could do. So I think that in addition to looking at new drugs, we need to look at evidence-based new diets to see if they can reduce morbidity and mortality in heart failure," Dr. Roger Corder said in presenting the chocolate study results at the annual scientific sessions of the American Heart Association.

The likely mechanism of benefit in heart failure patients involves a dark chocolate–induced reduction in endothelial dysfunction.

"Prior studies show consumption of cocoa flavonols in daily doses of 750 mg or more improve endothelial function in patients with coronary artery disease, in healthy subjects, and in diabetics," noted Dr. Corder of Queen Mary University of London.

The study involved 32 patients with stable heart failure on maximal medical therapy, all of whom had a history of ischemic heart disease. They were randomized to daily consumption of a 50-g bar of high-flavonol chocolate or a low-flavonol chocolate bar for 4 weeks, then crossed over to daily consumption of the other bar for another 4 weeks.

The test product contained 1,094 mg of flavonols per bar, while the low-flavonol comparator contained 95 mg. The high-flavonol chocolate bar was a custom-made product whose flavonol content far exceeds anything on the market. Dr. Corder and coinvestigators tested 50 brands of commercially available dark chocolate bars averaging 76% cocoa solids and determined their average flavonol content was 312 mg/50 g.

The study end points were change in diastolic blood pressure and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels after 4 weeks of eating each type of chocolate bar.

Twenty-four patients completed the study. Mean NT-proBNP dropped by an average of 39% from a baseline of 200 pmol/L after 4 weeks of eating the high-flavonol chocolate.

"Given that other trials of medications, including angiotensin receptor blockers, have shown a 30% reduction in NT-proBNP is associated with improved clinical outcomes, this looks to us like something of interest to pursue further with additional clinical studies. It’s worth noting that 12 of the 24 patients had a drop in NT-proBNP of 30% or more," Dr. Corder said.

From a baseline blood pressure of 126/71 mm Hg, diastolic pressure fell by 5 mm Hg in conjunction with consumption of the high-flavonol bar. Systolic pressure did not change significantly. Maintenance of systolic blood pressure with a reduction in diastolic pressure implies an increase in cardiac output – "and that would really be the optimum thing to have happened," he continued.

The low-flavonol chocolate bar did not produce changes in blood pressure or NT-proBNP.

A couple of down sides with the experimental high-flavonol chocolate bar emerged during the study. One was taste. Three of the eight study dropouts quit because they found the product’s taste unacceptable, while the others left for reasons unrelated to the study.

"We had an issue with taste. Even the patients who finished the study didn’t like the taste. There may be other countries where dark chocolate is popular, but the East of London would rather have their sweet milk chocolate than dark chocolate," according to Dr. Corder.

Weight gain is another concern. Both chocolate bars contained about 19 g of fat, including 12 g of saturated fat, per 50-g serving, with about 260 calories. From a baseline body weight of 85.7 kg, participants gained roughly 0.3 kg over the course of 4 weeks.

"In terms of long-term therapy, it may not be suitable to take dark chocolate on a daily basis at this level," he said.

However, food scientists involved in the study are tweaking the recipe to improve the taste of the superhigh-flavonol bar. There is also the option of extracting the flavonols and placing them in some other nutraceutical food product.

The study was funded by Swiss chocolate giant Barry Callebaut. Dr. Corder reported receiving a significant research grant from the company.

LOS ANGELES – There are perfectly good reasons for hospitals to offer elective percutaneous coronary intervention without on-site cardiac surgery backup, but saving institutional dollars isn't among them.

That's the bottom line from CPORT-E (Cardiovascular Patient Outcomes Research Team/Non-Primary Percutaneous Coronary Intervention Economic Study), the prespecified economic analysis conducted as part of the landmark CPORT trial.

Bruce Jancin/IMNG Medical Media

The estimated medical costs per CPORT participant, including the index revascularization and hospitalization as well as costs incurred during 9 months of follow-up, averaged $29,136 in hospitals without on-site coronary artery bypass surgery backup and $25,412 in centers with backup. This 15% difference did not reach statistical significance, Eric L. Eisenstein, DBA, reported at the annual scientific sessions of the American Heart Association.

Patients assigned to PCI at hospitals without on-site cardiac surgery actually had a shorter average length of stay; however, their total hospitalization costs ran higher because the study protocol dictated that their post-PCI care take place in the intensive care unit. Patients in centers with no on-site CABG backup also had a significantly higher rate of repeat target vessel revascularization during 9 months of follow-up: 6.5% compared with 5.4% when PCI was performed in hospitals with surgical backup, explained Dr. Eisenstein of Duke Clinical Research Institute, Durham, N.C.

CPORT was a randomized, prospective, multicenter trial in which the outcomes of elective PCI performed at hospitals with or without on-site cardiac surgery backup were compared for nearly 19,000 participants. As previously reported (N. Engl. J. Med. 2012; 366:1792-802), there were no significant differences between the two patient populations in terms of the co–primary end points of 6-week mortality (0.9% at hospitals without on-site surgery and 1.0% at those with backup) and 9-month major adverse cardiac events (12.1% without versus 11.2% with on-site surgical backup).

Discussant Dr. Mark A. Hlatky noted that 9-month total costs in CPORT-E were 22% higher at low-PCI-volume sites without surgery but only 7% higher at high-volume sites without surgery than at hospitals having on-site CABG backup.

"That’s a very interesting issue: The crucial factor driving costs may not be whether surgery is present on site or not, but the PCI volume at the site. If we have a low-volume site there may be higher costs and more adverse events. Whenever you do something in higher volumes you’re more efficient economically and you may actually do a little bit better job," said Dr. Hlatky, professor of health research and policy and of cardiovascular medicine at Stanford (Calif.) University.

As a matter of health policy, introducing elective PCI at hospitals without on-site cardiac surgery is attractive because it improves access, particularly for patients in rural areas where the nearest medical center with surgical backup may be a considerable distance away. Another consideration is that these centers without on-site surgery may be available for emergency PCI, thereby avoiding the delays inherent in patient transfer to a distant center, he observed.

Discussant Dr. David O. Williams pronounced CPORT "an extremely well-organized and well-conducted trial. It was a large study and the findings, I believe, are quite valid. To be applicable, however, hospitals will need to replicate all the necessary operational and training activities inherent in the trial, which were really quite extensive."

That means not taking money-saving shortcuts, such as eliminating the post-PCI stay in the ICU.

"I do believe this trial is significant and will likely impact the manner in which PCI is performed in the U.S. The performance of PCI in hospitals without on-site CABG surgery, I believe, will be adopted and become the standard of care," predicted Dr. Williams, an interventional cardiologist at Brigham and Women’s Hospital, Boston.

The CPORT-E study was funded by Johns Hopkins University. Dr. Eisenstein reported receiving research grants from Medtronic and Eli Lilly. Dr. Williams is the recipient of research grants from medical device companies. Dr. Hlatky reported having no relevant financial interests.

LOS ANGELES – There are perfectly good reasons for hospitals to offer elective percutaneous coronary intervention without on-site cardiac surgery backup, but saving institutional dollars isn't among them.

That's the bottom line from CPORT-E (Cardiovascular Patient Outcomes Research Team/Non-Primary Percutaneous Coronary Intervention Economic Study), the prespecified economic analysis conducted as part of the landmark CPORT trial.

Bruce Jancin/IMNG Medical Media

The estimated medical costs per CPORT participant, including the index revascularization and hospitalization as well as costs incurred during 9 months of follow-up, averaged $29,136 in hospitals without on-site coronary artery bypass surgery backup and $25,412 in centers with backup. This 15% difference did not reach statistical significance, Eric L. Eisenstein, DBA, reported at the annual scientific sessions of the American Heart Association.

Patients assigned to PCI at hospitals without on-site cardiac surgery actually had a shorter average length of stay; however, their total hospitalization costs ran higher because the study protocol dictated that their post-PCI care take place in the intensive care unit. Patients in centers with no on-site CABG backup also had a significantly higher rate of repeat target vessel revascularization during 9 months of follow-up: 6.5% compared with 5.4% when PCI was performed in hospitals with surgical backup, explained Dr. Eisenstein of Duke Clinical Research Institute, Durham, N.C.

CPORT was a randomized, prospective, multicenter trial in which the outcomes of elective PCI performed at hospitals with or without on-site cardiac surgery backup were compared for nearly 19,000 participants. As previously reported (N. Engl. J. Med. 2012; 366:1792-802), there were no significant differences between the two patient populations in terms of the co–primary end points of 6-week mortality (0.9% at hospitals without on-site surgery and 1.0% at those with backup) and 9-month major adverse cardiac events (12.1% without versus 11.2% with on-site surgical backup).

Discussant Dr. Mark A. Hlatky noted that 9-month total costs in CPORT-E were 22% higher at low-PCI-volume sites without surgery but only 7% higher at high-volume sites without surgery than at hospitals having on-site CABG backup.

"That’s a very interesting issue: The crucial factor driving costs may not be whether surgery is present on site or not, but the PCI volume at the site. If we have a low-volume site there may be higher costs and more adverse events. Whenever you do something in higher volumes you’re more efficient economically and you may actually do a little bit better job," said Dr. Hlatky, professor of health research and policy and of cardiovascular medicine at Stanford (Calif.) University.

As a matter of health policy, introducing elective PCI at hospitals without on-site cardiac surgery is attractive because it improves access, particularly for patients in rural areas where the nearest medical center with surgical backup may be a considerable distance away. Another consideration is that these centers without on-site surgery may be available for emergency PCI, thereby avoiding the delays inherent in patient transfer to a distant center, he observed.

Discussant Dr. David O. Williams pronounced CPORT "an extremely well-organized and well-conducted trial. It was a large study and the findings, I believe, are quite valid. To be applicable, however, hospitals will need to replicate all the necessary operational and training activities inherent in the trial, which were really quite extensive."

That means not taking money-saving shortcuts, such as eliminating the post-PCI stay in the ICU.

"I do believe this trial is significant and will likely impact the manner in which PCI is performed in the U.S. The performance of PCI in hospitals without on-site CABG surgery, I believe, will be adopted and become the standard of care," predicted Dr. Williams, an interventional cardiologist at Brigham and Women’s Hospital, Boston.

The CPORT-E study was funded by Johns Hopkins University. Dr. Eisenstein reported receiving research grants from Medtronic and Eli Lilly. Dr. Williams is the recipient of research grants from medical device companies. Dr. Hlatky reported having no relevant financial interests.

LOS ANGELES – There are perfectly good reasons for hospitals to offer elective percutaneous coronary intervention without on-site cardiac surgery backup, but saving institutional dollars isn't among them.

That's the bottom line from CPORT-E (Cardiovascular Patient Outcomes Research Team/Non-Primary Percutaneous Coronary Intervention Economic Study), the prespecified economic analysis conducted as part of the landmark CPORT trial.

Bruce Jancin/IMNG Medical Media

The estimated medical costs per CPORT participant, including the index revascularization and hospitalization as well as costs incurred during 9 months of follow-up, averaged $29,136 in hospitals without on-site coronary artery bypass surgery backup and $25,412 in centers with backup. This 15% difference did not reach statistical significance, Eric L. Eisenstein, DBA, reported at the annual scientific sessions of the American Heart Association.

Patients assigned to PCI at hospitals without on-site cardiac surgery actually had a shorter average length of stay; however, their total hospitalization costs ran higher because the study protocol dictated that their post-PCI care take place in the intensive care unit. Patients in centers with no on-site CABG backup also had a significantly higher rate of repeat target vessel revascularization during 9 months of follow-up: 6.5% compared with 5.4% when PCI was performed in hospitals with surgical backup, explained Dr. Eisenstein of Duke Clinical Research Institute, Durham, N.C.

CPORT was a randomized, prospective, multicenter trial in which the outcomes of elective PCI performed at hospitals with or without on-site cardiac surgery backup were compared for nearly 19,000 participants. As previously reported (N. Engl. J. Med. 2012; 366:1792-802), there were no significant differences between the two patient populations in terms of the co–primary end points of 6-week mortality (0.9% at hospitals without on-site surgery and 1.0% at those with backup) and 9-month major adverse cardiac events (12.1% without versus 11.2% with on-site surgical backup).

Discussant Dr. Mark A. Hlatky noted that 9-month total costs in CPORT-E were 22% higher at low-PCI-volume sites without surgery but only 7% higher at high-volume sites without surgery than at hospitals having on-site CABG backup.

"That’s a very interesting issue: The crucial factor driving costs may not be whether surgery is present on site or not, but the PCI volume at the site. If we have a low-volume site there may be higher costs and more adverse events. Whenever you do something in higher volumes you’re more efficient economically and you may actually do a little bit better job," said Dr. Hlatky, professor of health research and policy and of cardiovascular medicine at Stanford (Calif.) University.

As a matter of health policy, introducing elective PCI at hospitals without on-site cardiac surgery is attractive because it improves access, particularly for patients in rural areas where the nearest medical center with surgical backup may be a considerable distance away. Another consideration is that these centers without on-site surgery may be available for emergency PCI, thereby avoiding the delays inherent in patient transfer to a distant center, he observed.

Discussant Dr. David O. Williams pronounced CPORT "an extremely well-organized and well-conducted trial. It was a large study and the findings, I believe, are quite valid. To be applicable, however, hospitals will need to replicate all the necessary operational and training activities inherent in the trial, which were really quite extensive."

That means not taking money-saving shortcuts, such as eliminating the post-PCI stay in the ICU.

"I do believe this trial is significant and will likely impact the manner in which PCI is performed in the U.S. The performance of PCI in hospitals without on-site CABG surgery, I believe, will be adopted and become the standard of care," predicted Dr. Williams, an interventional cardiologist at Brigham and Women’s Hospital, Boston.

The CPORT-E study was funded by Johns Hopkins University. Dr. Eisenstein reported receiving research grants from Medtronic and Eli Lilly. Dr. Williams is the recipient of research grants from medical device companies. Dr. Hlatky reported having no relevant financial interests.

DENVER – Results of the first-ever head-to-head comparison of MRI vs. CT for diagnosis of occult hip fractures in the elderly show MRI to be the unequivocal winner.

"The take-home message is clear: MRI is the study of choice in this setting. If you suspect hip fracture in a patient whose plain films are difficult to interpret, get advanced imaging. Push for MRI," Dr. William K. Mallon said in his annual standing-room-only talk on recent highlights in the literature at the annual meeting of the American College of Emergency Physicians.

This study by investigators at the University of California, San Francisco’s Fresno campus earned a spot on Dr. Mallon’s short list of papers published in the last year with which he believes every emergency physician should be familiar. That’s because hip fracture in the elderly is such a common problem in community hospital EDs as well as trauma centers. It’s estimated that 4% of all hip fractures in the elderly are occult, meaning not diagnosable by plain x-ray.

"If you think you’re going to encounter 25 broken hips in your career, you’re going to encounter an occult fracture, so this is an important issue," observed Dr. Mallon of the University of Southern California, Los Angeles.

The study involved 235 patients aged 60 years and over with hip fracture, 211 of which were apparent on plain films. Of the 24 occult fractures, MRI detected 4 that 64-slice CT missed (J. Emerg. Med. 2012;43:303-7).

In his animated and entertaining talk before a capacity audience in the largest hall in the convention center, Dr. Mallon steered clear of articles published in the Annals of Emergency Medicine, reasoning that board-certified emergency physicians have already seen them. Here are some of his top picks from other journals on key topics:

• ALARA: This is an acronym for ‘As Low as Reasonably Achievable’ radiation exposure.

"I believe that in the year 2050, they’ll look back at us as the barbarians of our day, shamelessly and heedlessly irradiating an entire generation and causing cancer," Dr. Mallon declared. "They’re going to say, ‘Did they not think about what happened in Hiroshima? You can’t get away with this radiation crap.’ "

ALARA is not about finding workable alternatives to CT, such as ultrasound, whenever possible. That’s a given. It’s about developing lower-radiation methods of CT when nothing but CT will do. One commercially available low-radiation-exposure device, known as the Lodox Statscan, is on line at L.A. CountyUSC Medical Center, where Dr. Mallon practices.

"It’ll do a whole body AP and lateral in a multisystem trauma patient for less radiation than a chest x-ray," he noted.

Dr. Mallon singled out as one of the past year’s most provocative studies a South Korean trial in which 891 patients with suspected acute appendicitis were randomized single-blind to diagnostic evaluation using either low-dose or standard-dose CT. The low-dose group received 116 mGy/cm, a radiation exposure 80% less than in the standard-dose arm.

"This paper asks, with 80% less zap, can you still make the diagnosis? And the answer is yes," he said.

The negative appendectomy rate was 3.5% in the low-dose group and not statistically different at 3.2% in the standard-dose group. The perforation rate was 26.5% in the low-dose group and 23.3% with regular CT imaging.

Low-dose abdominal CT yields grainier images than physicians are accustomed to. Yet the 3.2% secondary imaging rate in the low-dose group wasn’t statistically different from that in the standard-dose arm (N. Engl. J. Med. 2012;366:1596-605).

This study will have to be replicated in the United States before American radiologists and surgeons will accept low-radiation CT to rule out appendicitis. The academic community must lead the way here, in Dr. Mallon’s view.

"As an emergency physician, I think I can easily live with those numbers, if they are the real numbers. We could start now with lower-radiation protocols. I think this is an important thing, and if we as a specialty aren’t going to advocate and push for it, I just think it’ll stay status quo forever," he added.

• Pulmonary embolism overdiagnosis: Pulmonary embolism, in Dr. Mallon’s view, is the bane of the emergency department, a double-edged sword.

"If you miss the diagnosis, they could die of the next one. And if you diagnose it and treat it, they risk serious anticoagulation-related complications. The fact is, the most dangerous inpatient drug in terms of serious, life-threatening complications is heparin. And the most dangerous outpatient drug in all of medicine in terms of serious, life-threatening complications is Coumadin," he asserted.

An analysis of time trends in pulmonary embolism (PE) in the United States nicely captured his frustration on this score, thereby making his ‘best-of’ list. The investigators compared national rates of PE and treatment outcomes before and after 1988, the year that CT pulmonary angiography became widely available. After 1988, the incidence of PE climbed by 81% through 2006, and the rate of in-hospital anticoagulation-related complications rose by 71%, from 3.1 to 5.3 cases per 100,000. Yet there was no significant reduction in the death rate due to PE (Arch. Intern. Med. 2011;171:831-7).

"Ouch! All we’ve done is harm a lot more people without a lot of evidence that we’ve saved more people," Dr. Mallon commented.

"I remember when I was in medical school I was told this: If a person has a PE of significance, they will have the diagnostic duet of tachypnea and tachycardia. They’ll be sick from their PE. And PE morphed from that life-threatening thing to us finding these small, subsegmental little things we don’t even really know the meaning of in a person with a totally normal ECG who maybe had a twinge of chest pain and couldn’t catch their breath for 5 minutes," he said. "I think there’s compelling evidence that what we used to think a PE was is not what PE is today, and that the need for treatment of these newer PEs isn’t being talked about in a sensible way. There’s room for that discussion."

• Hyperbaric oxygen therapy for carbon monoxide poisoning: The hyperbaric oxygen chamber is well accepted as standard therapy for divers with the bends, but its utility in cases of domestic acute carbon monoxide toxicity has been highly controversial. A pair of recent French prospective randomized trials concluded it is ineffective and possibly harmful.

One study randomized 179 noncomatose patients with transient loss of consciousness to a real or sham hyperbaric oxygen therapy session. There was no difference in outcomes.

The other trial involved 206 comatose carbon monoxide overdose patients randomized to one or two sessions of hyperbaric oxygen therapy. It was halted early because the group that received more hyperbaric oxygen had less complete recovery, worse delayed neurologic symptoms, and more persistent sequelae (Intensive Care Med. 2011;37:486-92).

• Nonsurgical hemorrhage control: Hyperfibrinolysis is present in 10%-15% of trauma patients and is associated with sharply higher 6- and 24-hour mortality. It can now be detected in 15 minutes at the bedside using thromboelastogram measurement. And, in several recent studies, early administration of tranexamic acid to trauma patients in order to block hyperfibrinolysis has demonstrated improved survival.

The most recent of these studies, MATTERS, (Military Application of Tranexamic Acid in Trauma Emergency Resuscitation), was a retrospective observational study that included 896 trauma patients who received packed red blood cells, 293 of whom also received tranexamic acid.

Unadjusted mortality was significantly lower in tranexamic acid recipients by a margin of 17.4%, compared with 23.9%, even though they had higher mean Injury Severity Scores and thus should have done worse.

The survival benefit associated with tranexamic acid was greatest in the subgroup who received massive transfusions. Their mortality rate was 14.4% compared to 28.1% in controls. In a multivariate analysis, administration of tranexamic acid in this subgroup was associated with a 7.2-fold increased likelihood of survival (Arch. Surg. 2012;147:113-9).

Tranexamic acid is a relatively inexpensive, Food and Drug Administration–approved synthetic blocker of the conversion of plasminogen to plasmin. It has a reasonable safety profile. Remaining questions regarding its incorporation into trauma management protocols include optimal dosing and whether thromboelastogram measurement should be used to guide therapy such that only those patients with hyperfibrinolysis would get tranexamic acid.

Look for answers to come from two ongoing major randomized trials: CRASH-3 (Clinical Randomisation of an Antifibrinolytic in Significant Head Injury) and PROPPR (Pragmatic, Randomized Optimal Platelets and Plasma Ratios), Dr. Mallon said.

• ‘ARDS, acronyms, and the Pinocchio effect’: This was the title of an essay by British physicians (Anaesthesia 2010; 65: 976-9) who argued that the medical world has gone acronym-crazy, with vast research money being spent trying to find cures for ARDS (acute respiratory distress syndrome), SIRS (systemic inflammatory response syndrome), ARF (acute respiratory failure), and the like.

"This is the oldest paper in the series, but I thought it was important enough to bring up," Dr. Mallon explained. "The Pinocchio effect is an important new concept in medicine. The authors point out that these aren’t diseases, they’re just acronyms. When you look at ARDS or SIRS, there are dozens of causes of each of them. Why on earth would we think there’s going to be a magic bullet therapy when there’s such tremendous underlying heterogeneity in the cause? Yet, we keep doing research trials trying to find a treatment for SIRS or ARDS."

"These authors point out, ‘Pinocchio, you’re lying. Organ failure is not a specific diagnosis but a constellation of signs and symptoms.’ We’ve got to stop lying to ourselves that there’s going to be a unifying therapy," Dr. Mallon said.

He reported having no financial conflicts.

DENVER – Results of the first-ever head-to-head comparison of MRI vs. CT for diagnosis of occult hip fractures in the elderly show MRI to be the unequivocal winner.

"The take-home message is clear: MRI is the study of choice in this setting. If you suspect hip fracture in a patient whose plain films are difficult to interpret, get advanced imaging. Push for MRI," Dr. William K. Mallon said in his annual standing-room-only talk on recent highlights in the literature at the annual meeting of the American College of Emergency Physicians.

This study by investigators at the University of California, San Francisco’s Fresno campus earned a spot on Dr. Mallon’s short list of papers published in the last year with which he believes every emergency physician should be familiar. That’s because hip fracture in the elderly is such a common problem in community hospital EDs as well as trauma centers. It’s estimated that 4% of all hip fractures in the elderly are occult, meaning not diagnosable by plain x-ray.

"If you think you’re going to encounter 25 broken hips in your career, you’re going to encounter an occult fracture, so this is an important issue," observed Dr. Mallon of the University of Southern California, Los Angeles.

The study involved 235 patients aged 60 years and over with hip fracture, 211 of which were apparent on plain films. Of the 24 occult fractures, MRI detected 4 that 64-slice CT missed (J. Emerg. Med. 2012;43:303-7).

In his animated and entertaining talk before a capacity audience in the largest hall in the convention center, Dr. Mallon steered clear of articles published in the Annals of Emergency Medicine, reasoning that board-certified emergency physicians have already seen them. Here are some of his top picks from other journals on key topics:

• ALARA: This is an acronym for ‘As Low as Reasonably Achievable’ radiation exposure.

"I believe that in the year 2050, they’ll look back at us as the barbarians of our day, shamelessly and heedlessly irradiating an entire generation and causing cancer," Dr. Mallon declared. "They’re going to say, ‘Did they not think about what happened in Hiroshima? You can’t get away with this radiation crap.’ "

ALARA is not about finding workable alternatives to CT, such as ultrasound, whenever possible. That’s a given. It’s about developing lower-radiation methods of CT when nothing but CT will do. One commercially available low-radiation-exposure device, known as the Lodox Statscan, is on line at L.A. CountyUSC Medical Center, where Dr. Mallon practices.

"It’ll do a whole body AP and lateral in a multisystem trauma patient for less radiation than a chest x-ray," he noted.

Dr. Mallon singled out as one of the past year’s most provocative studies a South Korean trial in which 891 patients with suspected acute appendicitis were randomized single-blind to diagnostic evaluation using either low-dose or standard-dose CT. The low-dose group received 116 mGy/cm, a radiation exposure 80% less than in the standard-dose arm.

"This paper asks, with 80% less zap, can you still make the diagnosis? And the answer is yes," he said.

The negative appendectomy rate was 3.5% in the low-dose group and not statistically different at 3.2% in the standard-dose group. The perforation rate was 26.5% in the low-dose group and 23.3% with regular CT imaging.

Low-dose abdominal CT yields grainier images than physicians are accustomed to. Yet the 3.2% secondary imaging rate in the low-dose group wasn’t statistically different from that in the standard-dose arm (N. Engl. J. Med. 2012;366:1596-605).

This study will have to be replicated in the United States before American radiologists and surgeons will accept low-radiation CT to rule out appendicitis. The academic community must lead the way here, in Dr. Mallon’s view.

"As an emergency physician, I think I can easily live with those numbers, if they are the real numbers. We could start now with lower-radiation protocols. I think this is an important thing, and if we as a specialty aren’t going to advocate and push for it, I just think it’ll stay status quo forever," he added.

• Pulmonary embolism overdiagnosis: Pulmonary embolism, in Dr. Mallon’s view, is the bane of the emergency department, a double-edged sword.

"If you miss the diagnosis, they could die of the next one. And if you diagnose it and treat it, they risk serious anticoagulation-related complications. The fact is, the most dangerous inpatient drug in terms of serious, life-threatening complications is heparin. And the most dangerous outpatient drug in all of medicine in terms of serious, life-threatening complications is Coumadin," he asserted.

An analysis of time trends in pulmonary embolism (PE) in the United States nicely captured his frustration on this score, thereby making his ‘best-of’ list. The investigators compared national rates of PE and treatment outcomes before and after 1988, the year that CT pulmonary angiography became widely available. After 1988, the incidence of PE climbed by 81% through 2006, and the rate of in-hospital anticoagulation-related complications rose by 71%, from 3.1 to 5.3 cases per 100,000. Yet there was no significant reduction in the death rate due to PE (Arch. Intern. Med. 2011;171:831-7).

"Ouch! All we’ve done is harm a lot more people without a lot of evidence that we’ve saved more people," Dr. Mallon commented.

"I remember when I was in medical school I was told this: If a person has a PE of significance, they will have the diagnostic duet of tachypnea and tachycardia. They’ll be sick from their PE. And PE morphed from that life-threatening thing to us finding these small, subsegmental little things we don’t even really know the meaning of in a person with a totally normal ECG who maybe had a twinge of chest pain and couldn’t catch their breath for 5 minutes," he said. "I think there’s compelling evidence that what we used to think a PE was is not what PE is today, and that the need for treatment of these newer PEs isn’t being talked about in a sensible way. There’s room for that discussion."

• Hyperbaric oxygen therapy for carbon monoxide poisoning: The hyperbaric oxygen chamber is well accepted as standard therapy for divers with the bends, but its utility in cases of domestic acute carbon monoxide toxicity has been highly controversial. A pair of recent French prospective randomized trials concluded it is ineffective and possibly harmful.

One study randomized 179 noncomatose patients with transient loss of consciousness to a real or sham hyperbaric oxygen therapy session. There was no difference in outcomes.

The other trial involved 206 comatose carbon monoxide overdose patients randomized to one or two sessions of hyperbaric oxygen therapy. It was halted early because the group that received more hyperbaric oxygen had less complete recovery, worse delayed neurologic symptoms, and more persistent sequelae (Intensive Care Med. 2011;37:486-92).

• Nonsurgical hemorrhage control: Hyperfibrinolysis is present in 10%-15% of trauma patients and is associated with sharply higher 6- and 24-hour mortality. It can now be detected in 15 minutes at the bedside using thromboelastogram measurement. And, in several recent studies, early administration of tranexamic acid to trauma patients in order to block hyperfibrinolysis has demonstrated improved survival.

The most recent of these studies, MATTERS, (Military Application of Tranexamic Acid in Trauma Emergency Resuscitation), was a retrospective observational study that included 896 trauma patients who received packed red blood cells, 293 of whom also received tranexamic acid.

Unadjusted mortality was significantly lower in tranexamic acid recipients by a margin of 17.4%, compared with 23.9%, even though they had higher mean Injury Severity Scores and thus should have done worse.

The survival benefit associated with tranexamic acid was greatest in the subgroup who received massive transfusions. Their mortality rate was 14.4% compared to 28.1% in controls. In a multivariate analysis, administration of tranexamic acid in this subgroup was associated with a 7.2-fold increased likelihood of survival (Arch. Surg. 2012;147:113-9).

Tranexamic acid is a relatively inexpensive, Food and Drug Administration–approved synthetic blocker of the conversion of plasminogen to plasmin. It has a reasonable safety profile. Remaining questions regarding its incorporation into trauma management protocols include optimal dosing and whether thromboelastogram measurement should be used to guide therapy such that only those patients with hyperfibrinolysis would get tranexamic acid.

Look for answers to come from two ongoing major randomized trials: CRASH-3 (Clinical Randomisation of an Antifibrinolytic in Significant Head Injury) and PROPPR (Pragmatic, Randomized Optimal Platelets and Plasma Ratios), Dr. Mallon said.

• ‘ARDS, acronyms, and the Pinocchio effect’: This was the title of an essay by British physicians (Anaesthesia 2010; 65: 976-9) who argued that the medical world has gone acronym-crazy, with vast research money being spent trying to find cures for ARDS (acute respiratory distress syndrome), SIRS (systemic inflammatory response syndrome), ARF (acute respiratory failure), and the like.

"This is the oldest paper in the series, but I thought it was important enough to bring up," Dr. Mallon explained. "The Pinocchio effect is an important new concept in medicine. The authors point out that these aren’t diseases, they’re just acronyms. When you look at ARDS or SIRS, there are dozens of causes of each of them. Why on earth would we think there’s going to be a magic bullet therapy when there’s such tremendous underlying heterogeneity in the cause? Yet, we keep doing research trials trying to find a treatment for SIRS or ARDS."

"These authors point out, ‘Pinocchio, you’re lying. Organ failure is not a specific diagnosis but a constellation of signs and symptoms.’ We’ve got to stop lying to ourselves that there’s going to be a unifying therapy," Dr. Mallon said.

He reported having no financial conflicts.

DENVER – Results of the first-ever head-to-head comparison of MRI vs. CT for diagnosis of occult hip fractures in the elderly show MRI to be the unequivocal winner.

"The take-home message is clear: MRI is the study of choice in this setting. If you suspect hip fracture in a patient whose plain films are difficult to interpret, get advanced imaging. Push for MRI," Dr. William K. Mallon said in his annual standing-room-only talk on recent highlights in the literature at the annual meeting of the American College of Emergency Physicians.

This study by investigators at the University of California, San Francisco’s Fresno campus earned a spot on Dr. Mallon’s short list of papers published in the last year with which he believes every emergency physician should be familiar. That’s because hip fracture in the elderly is such a common problem in community hospital EDs as well as trauma centers. It’s estimated that 4% of all hip fractures in the elderly are occult, meaning not diagnosable by plain x-ray.

"If you think you’re going to encounter 25 broken hips in your career, you’re going to encounter an occult fracture, so this is an important issue," observed Dr. Mallon of the University of Southern California, Los Angeles.

The study involved 235 patients aged 60 years and over with hip fracture, 211 of which were apparent on plain films. Of the 24 occult fractures, MRI detected 4 that 64-slice CT missed (J. Emerg. Med. 2012;43:303-7).

In his animated and entertaining talk before a capacity audience in the largest hall in the convention center, Dr. Mallon steered clear of articles published in the Annals of Emergency Medicine, reasoning that board-certified emergency physicians have already seen them. Here are some of his top picks from other journals on key topics:

• ALARA: This is an acronym for ‘As Low as Reasonably Achievable’ radiation exposure.

"I believe that in the year 2050, they’ll look back at us as the barbarians of our day, shamelessly and heedlessly irradiating an entire generation and causing cancer," Dr. Mallon declared. "They’re going to say, ‘Did they not think about what happened in Hiroshima? You can’t get away with this radiation crap.’ "

ALARA is not about finding workable alternatives to CT, such as ultrasound, whenever possible. That’s a given. It’s about developing lower-radiation methods of CT when nothing but CT will do. One commercially available low-radiation-exposure device, known as the Lodox Statscan, is on line at L.A. CountyUSC Medical Center, where Dr. Mallon practices.

"It’ll do a whole body AP and lateral in a multisystem trauma patient for less radiation than a chest x-ray," he noted.

Dr. Mallon singled out as one of the past year’s most provocative studies a South Korean trial in which 891 patients with suspected acute appendicitis were randomized single-blind to diagnostic evaluation using either low-dose or standard-dose CT. The low-dose group received 116 mGy/cm, a radiation exposure 80% less than in the standard-dose arm.

"This paper asks, with 80% less zap, can you still make the diagnosis? And the answer is yes," he said.

The negative appendectomy rate was 3.5% in the low-dose group and not statistically different at 3.2% in the standard-dose group. The perforation rate was 26.5% in the low-dose group and 23.3% with regular CT imaging.

Low-dose abdominal CT yields grainier images than physicians are accustomed to. Yet the 3.2% secondary imaging rate in the low-dose group wasn’t statistically different from that in the standard-dose arm (N. Engl. J. Med. 2012;366:1596-605).

This study will have to be replicated in the United States before American radiologists and surgeons will accept low-radiation CT to rule out appendicitis. The academic community must lead the way here, in Dr. Mallon’s view.

"As an emergency physician, I think I can easily live with those numbers, if they are the real numbers. We could start now with lower-radiation protocols. I think this is an important thing, and if we as a specialty aren’t going to advocate and push for it, I just think it’ll stay status quo forever," he added.

• Pulmonary embolism overdiagnosis: Pulmonary embolism, in Dr. Mallon’s view, is the bane of the emergency department, a double-edged sword.

"If you miss the diagnosis, they could die of the next one. And if you diagnose it and treat it, they risk serious anticoagulation-related complications. The fact is, the most dangerous inpatient drug in terms of serious, life-threatening complications is heparin. And the most dangerous outpatient drug in all of medicine in terms of serious, life-threatening complications is Coumadin," he asserted.

An analysis of time trends in pulmonary embolism (PE) in the United States nicely captured his frustration on this score, thereby making his ‘best-of’ list. The investigators compared national rates of PE and treatment outcomes before and after 1988, the year that CT pulmonary angiography became widely available. After 1988, the incidence of PE climbed by 81% through 2006, and the rate of in-hospital anticoagulation-related complications rose by 71%, from 3.1 to 5.3 cases per 100,000. Yet there was no significant reduction in the death rate due to PE (Arch. Intern. Med. 2011;171:831-7).

"Ouch! All we’ve done is harm a lot more people without a lot of evidence that we’ve saved more people," Dr. Mallon commented.

"I remember when I was in medical school I was told this: If a person has a PE of significance, they will have the diagnostic duet of tachypnea and tachycardia. They’ll be sick from their PE. And PE morphed from that life-threatening thing to us finding these small, subsegmental little things we don’t even really know the meaning of in a person with a totally normal ECG who maybe had a twinge of chest pain and couldn’t catch their breath for 5 minutes," he said. "I think there’s compelling evidence that what we used to think a PE was is not what PE is today, and that the need for treatment of these newer PEs isn’t being talked about in a sensible way. There’s room for that discussion."

• Hyperbaric oxygen therapy for carbon monoxide poisoning: The hyperbaric oxygen chamber is well accepted as standard therapy for divers with the bends, but its utility in cases of domestic acute carbon monoxide toxicity has been highly controversial. A pair of recent French prospective randomized trials concluded it is ineffective and possibly harmful.

One study randomized 179 noncomatose patients with transient loss of consciousness to a real or sham hyperbaric oxygen therapy session. There was no difference in outcomes.

The other trial involved 206 comatose carbon monoxide overdose patients randomized to one or two sessions of hyperbaric oxygen therapy. It was halted early because the group that received more hyperbaric oxygen had less complete recovery, worse delayed neurologic symptoms, and more persistent sequelae (Intensive Care Med. 2011;37:486-92).

• Nonsurgical hemorrhage control: Hyperfibrinolysis is present in 10%-15% of trauma patients and is associated with sharply higher 6- and 24-hour mortality. It can now be detected in 15 minutes at the bedside using thromboelastogram measurement. And, in several recent studies, early administration of tranexamic acid to trauma patients in order to block hyperfibrinolysis has demonstrated improved survival.

The most recent of these studies, MATTERS, (Military Application of Tranexamic Acid in Trauma Emergency Resuscitation), was a retrospective observational study that included 896 trauma patients who received packed red blood cells, 293 of whom also received tranexamic acid.

Unadjusted mortality was significantly lower in tranexamic acid recipients by a margin of 17.4%, compared with 23.9%, even though they had higher mean Injury Severity Scores and thus should have done worse.

The survival benefit associated with tranexamic acid was greatest in the subgroup who received massive transfusions. Their mortality rate was 14.4% compared to 28.1% in controls. In a multivariate analysis, administration of tranexamic acid in this subgroup was associated with a 7.2-fold increased likelihood of survival (Arch. Surg. 2012;147:113-9).

Tranexamic acid is a relatively inexpensive, Food and Drug Administration–approved synthetic blocker of the conversion of plasminogen to plasmin. It has a reasonable safety profile. Remaining questions regarding its incorporation into trauma management protocols include optimal dosing and whether thromboelastogram measurement should be used to guide therapy such that only those patients with hyperfibrinolysis would get tranexamic acid.

Look for answers to come from two ongoing major randomized trials: CRASH-3 (Clinical Randomisation of an Antifibrinolytic in Significant Head Injury) and PROPPR (Pragmatic, Randomized Optimal Platelets and Plasma Ratios), Dr. Mallon said.

• ‘ARDS, acronyms, and the Pinocchio effect’: This was the title of an essay by British physicians (Anaesthesia 2010; 65: 976-9) who argued that the medical world has gone acronym-crazy, with vast research money being spent trying to find cures for ARDS (acute respiratory distress syndrome), SIRS (systemic inflammatory response syndrome), ARF (acute respiratory failure), and the like.

"This is the oldest paper in the series, but I thought it was important enough to bring up," Dr. Mallon explained. "The Pinocchio effect is an important new concept in medicine. The authors point out that these aren’t diseases, they’re just acronyms. When you look at ARDS or SIRS, there are dozens of causes of each of them. Why on earth would we think there’s going to be a magic bullet therapy when there’s such tremendous underlying heterogeneity in the cause? Yet, we keep doing research trials trying to find a treatment for SIRS or ARDS."

"These authors point out, ‘Pinocchio, you’re lying. Organ failure is not a specific diagnosis but a constellation of signs and symptoms.’ We’ve got to stop lying to ourselves that there’s going to be a unifying therapy," Dr. Mallon said.

He reported having no financial conflicts.