Mary Ann Moon

For women with advanced epithelial ovarian cancer, aggressive cytoreductive surgery improves survival only if complete resection of disease is achieved. Aggressive debulking that achieves anything less than complete resection (R0) – even if the residual tumor is minimal (< 1 cm) – will not improve survival, according to a report published online Feb. 9 in Journal of Clinical Oncology.

“Over the last decade, there has been a growing trend toward more aggressive primary debulking surgery for women with epithelial ovarian cancer,” even though the impact of this approach on survival “has been unclear.” To examine the issue, researchers analyzed data from the multicenter Gynecologic Oncology Group-182 cohort, which they described as the largest clinical trial of ovarian cancer to date. They assessed survival outcomes in 2,655 patients who underwent aggressive cytoreductive surgery before receiving chemotherapy. The resection was complete (R0), in 32.4% of the women; it left minimal residual tumor (< 1 cm) in the remaining 67.6%, said Dr. Neil S. Horowitz of Brigham and Women’s Hospital, Boston, and his associates.

Both overall survival and progression-free survival were significantly improved when R0 was achieved, but not when there was minimal residual tumor. In the literature, as many as 25% of women who undergo aggressive surgical cytoreduction experience significant postoperative morbidity, and up to 2% fail to survive the procedure. These findings therefore “suggest that complex surgical procedures should be selectively used in patients with significant disease distribution and limited to those where only microscopic residual can be achieved,” the investigators said (J. Clin. Oncol. 2015 Feb. 9 [doi: 10.1200/JCO.2014.56.3106]).

“We suggest a potential paradigm shift, in which, if R0 is difficult to attain at primary cytoreduction, use of neoadjuvant chemotherapy with interval debulking to allow for R0 may be superior to primary surgery after which the patient is left with gross residual disease,” Dr. Horowitz and his associates added.

For women with advanced epithelial ovarian cancer, aggressive cytoreductive surgery improves survival only if complete resection of disease is achieved. Aggressive debulking that achieves anything less than complete resection (R0) – even if the residual tumor is minimal (< 1 cm) – will not improve survival, according to a report published online Feb. 9 in Journal of Clinical Oncology.

“Over the last decade, there has been a growing trend toward more aggressive primary debulking surgery for women with epithelial ovarian cancer,” even though the impact of this approach on survival “has been unclear.” To examine the issue, researchers analyzed data from the multicenter Gynecologic Oncology Group-182 cohort, which they described as the largest clinical trial of ovarian cancer to date. They assessed survival outcomes in 2,655 patients who underwent aggressive cytoreductive surgery before receiving chemotherapy. The resection was complete (R0), in 32.4% of the women; it left minimal residual tumor (< 1 cm) in the remaining 67.6%, said Dr. Neil S. Horowitz of Brigham and Women’s Hospital, Boston, and his associates.

Both overall survival and progression-free survival were significantly improved when R0 was achieved, but not when there was minimal residual tumor. In the literature, as many as 25% of women who undergo aggressive surgical cytoreduction experience significant postoperative morbidity, and up to 2% fail to survive the procedure. These findings therefore “suggest that complex surgical procedures should be selectively used in patients with significant disease distribution and limited to those where only microscopic residual can be achieved,” the investigators said (J. Clin. Oncol. 2015 Feb. 9 [doi: 10.1200/JCO.2014.56.3106]).

“We suggest a potential paradigm shift, in which, if R0 is difficult to attain at primary cytoreduction, use of neoadjuvant chemotherapy with interval debulking to allow for R0 may be superior to primary surgery after which the patient is left with gross residual disease,” Dr. Horowitz and his associates added.

For women with advanced epithelial ovarian cancer, aggressive cytoreductive surgery improves survival only if complete resection of disease is achieved. Aggressive debulking that achieves anything less than complete resection (R0) – even if the residual tumor is minimal (< 1 cm) – will not improve survival, according to a report published online Feb. 9 in Journal of Clinical Oncology.

“Over the last decade, there has been a growing trend toward more aggressive primary debulking surgery for women with epithelial ovarian cancer,” even though the impact of this approach on survival “has been unclear.” To examine the issue, researchers analyzed data from the multicenter Gynecologic Oncology Group-182 cohort, which they described as the largest clinical trial of ovarian cancer to date. They assessed survival outcomes in 2,655 patients who underwent aggressive cytoreductive surgery before receiving chemotherapy. The resection was complete (R0), in 32.4% of the women; it left minimal residual tumor (< 1 cm) in the remaining 67.6%, said Dr. Neil S. Horowitz of Brigham and Women’s Hospital, Boston, and his associates.

Both overall survival and progression-free survival were significantly improved when R0 was achieved, but not when there was minimal residual tumor. In the literature, as many as 25% of women who undergo aggressive surgical cytoreduction experience significant postoperative morbidity, and up to 2% fail to survive the procedure. These findings therefore “suggest that complex surgical procedures should be selectively used in patients with significant disease distribution and limited to those where only microscopic residual can be achieved,” the investigators said (J. Clin. Oncol. 2015 Feb. 9 [doi: 10.1200/JCO.2014.56.3106]).

“We suggest a potential paradigm shift, in which, if R0 is difficult to attain at primary cytoreduction, use of neoadjuvant chemotherapy with interval debulking to allow for R0 may be superior to primary surgery after which the patient is left with gross residual disease,” Dr. Horowitz and his associates added.

Smoking causes death from many diseases that until now have not been linked officially to tobacco use, including digestive disorders, liver cirrhosis, infections, renal failure, and breast and prostate cancers, according to a report published online Feb. 11 in the New England Journal of Medicine.

“Our results suggest that the number of persons in the United States who die each year as a result of smoking cigarettes may be substantially greater than currently estimated,” said Brian D. Carter of the epidemiology research program, American Cancer Society, Atlanta, and his associates.

The 2014 Surgeon General’s report estimated that smoking causes more than 480,000 deaths every year in the United States, based on mortality figures from 21 diseases that have been formally established as caused by smoking: 12 types of cancer, 6 types of cardiovascular disease, diabetes, chronic obstructive pulmonary disease, and pneumonia. Mr. Carter and his associates pooled data from five large cohort studies to examine possible associations between smoking and an additional 31 cause-of-death categories. They now estimate that an additional 60,000-120,000 deaths each year can be attributed to smoking.

For their study, the investigators assessed 421,378 men and 532,651 women aged 55 years and older at baseline whose smoking status was carefully recorded and who were followed from 2000 to 2011 in the Cancer Prevention Study II Nutrition Cohort, the Nurses’ Health Study I, the Health Professionals Follow-up Study, the Women’s Health Initiative, and the National Institutes of Health-AARP Diet and Health Study.

As expected, smokers had a twofold to threefold higher mortality from any cause, compared with nonsmokers. Smokers also had a markedly higher risk of death than nonsmokers from all 21 causes already established as attributable to tobacco use, such as lung cancer, oral cancer, ischemic heart disease, atherosclerosis, and stroke. But approximately 17% of smokers’ excess mortality was accounted for by several diseases that previously have not been attributable to tobacco use.

For example, the risk of death due to intestinal ischemia was approximately six times higher among smokers than among nonsmokers, a remarkably strong association that was also reported in the Million Women Study. “Smoking acutely reduces blood flow to the intestines, and evidence suggests that smoking causes risk factors that can often lead to intestinal ischemia, including atherosclerosis, platelet aggregation, and congestive heart failure,” Mr. Carter and his associates said (N. Engl. J. Med. 2015 Feb. 12 [doi:10.1056/NEJMsa140721]).  In this study, smoking also more than doubled the risk of dying from other digestive diseases. Previous studies have suggested a link between smoking and digestive disorders such as Crohn’s disease, peptic ulcers, acute pancreatitis, paralytic ileus, bowel obstruction, choletlithiasis, diverticulitis, and gastrointestinal hemorrhage. “Although these diseases are not common causes of death, they account for millions of hospitalizations each year,” the investigators noted.

Continue for mortality risks >>

The mortality risk from liver cirrhosis, after the data were adjusted to account for alcohol consumption, was more than three times higher in smokers than in nonsmokers. Even smokers who did not drink alcohol were at significantly increased risk of cirrhosis, compared with nonsmokers.

The risk of death due to infection was 2.3 times higher in smokers than in nonsmokers. This strong association was dose-dependent, as infection-related mortality rose with increasing smoking intensity. And among study participants who had quit smoking, infection-related mortality declined as the number of years since cessation increased.

The rate of death due to renal failure was twice as high among smokers as among nonsmokers. And the rate of death due to hypertensive heart disease, the only category of heart disease not already established as smoking related, was 2.4 times higher in smokers. The latter association “is relevant for assessing the public health burden of smoking, since a considerable number of deaths in the United States are attributable to hypertensive heart disease,” according to Mr. Carter and his associates.

Smoking also was strongly associated with “multiple diseases too uncommon to examine individually.” This included all rare cancers combined, rare digestive diseases, and respiratory diseases other than those already known to stem from smoking.

In women, smoking raised breast cancer mortality, with a relative risk of 1.3. This association was strongly dose dependent. In men, smoking raised prostate cancer mortality, with a relative risk of 1.4.

This study was limited in that most of the participants were white and better educated than the general population, which may affect the applicability of the results to other populations.

Smoking causes death from many diseases that until now have not been linked officially to tobacco use, including digestive disorders, liver cirrhosis, infections, renal failure, and breast and prostate cancers, according to a report published online Feb. 11 in the New England Journal of Medicine.

“Our results suggest that the number of persons in the United States who die each year as a result of smoking cigarettes may be substantially greater than currently estimated,” said Brian D. Carter of the epidemiology research program, American Cancer Society, Atlanta, and his associates.

The 2014 Surgeon General’s report estimated that smoking causes more than 480,000 deaths every year in the United States, based on mortality figures from 21 diseases that have been formally established as caused by smoking: 12 types of cancer, 6 types of cardiovascular disease, diabetes, chronic obstructive pulmonary disease, and pneumonia. Mr. Carter and his associates pooled data from five large cohort studies to examine possible associations between smoking and an additional 31 cause-of-death categories. They now estimate that an additional 60,000-120,000 deaths each year can be attributed to smoking.

For their study, the investigators assessed 421,378 men and 532,651 women aged 55 years and older at baseline whose smoking status was carefully recorded and who were followed from 2000 to 2011 in the Cancer Prevention Study II Nutrition Cohort, the Nurses’ Health Study I, the Health Professionals Follow-up Study, the Women’s Health Initiative, and the National Institutes of Health-AARP Diet and Health Study.

As expected, smokers had a twofold to threefold higher mortality from any cause, compared with nonsmokers. Smokers also had a markedly higher risk of death than nonsmokers from all 21 causes already established as attributable to tobacco use, such as lung cancer, oral cancer, ischemic heart disease, atherosclerosis, and stroke. But approximately 17% of smokers’ excess mortality was accounted for by several diseases that previously have not been attributable to tobacco use.

For example, the risk of death due to intestinal ischemia was approximately six times higher among smokers than among nonsmokers, a remarkably strong association that was also reported in the Million Women Study. “Smoking acutely reduces blood flow to the intestines, and evidence suggests that smoking causes risk factors that can often lead to intestinal ischemia, including atherosclerosis, platelet aggregation, and congestive heart failure,” Mr. Carter and his associates said (N. Engl. J. Med. 2015 Feb. 12 [doi:10.1056/NEJMsa140721]).  In this study, smoking also more than doubled the risk of dying from other digestive diseases. Previous studies have suggested a link between smoking and digestive disorders such as Crohn’s disease, peptic ulcers, acute pancreatitis, paralytic ileus, bowel obstruction, choletlithiasis, diverticulitis, and gastrointestinal hemorrhage. “Although these diseases are not common causes of death, they account for millions of hospitalizations each year,” the investigators noted.

Continue for mortality risks >>

The mortality risk from liver cirrhosis, after the data were adjusted to account for alcohol consumption, was more than three times higher in smokers than in nonsmokers. Even smokers who did not drink alcohol were at significantly increased risk of cirrhosis, compared with nonsmokers.

The risk of death due to infection was 2.3 times higher in smokers than in nonsmokers. This strong association was dose-dependent, as infection-related mortality rose with increasing smoking intensity. And among study participants who had quit smoking, infection-related mortality declined as the number of years since cessation increased.

The rate of death due to renal failure was twice as high among smokers as among nonsmokers. And the rate of death due to hypertensive heart disease, the only category of heart disease not already established as smoking related, was 2.4 times higher in smokers. The latter association “is relevant for assessing the public health burden of smoking, since a considerable number of deaths in the United States are attributable to hypertensive heart disease,” according to Mr. Carter and his associates.

Smoking also was strongly associated with “multiple diseases too uncommon to examine individually.” This included all rare cancers combined, rare digestive diseases, and respiratory diseases other than those already known to stem from smoking.

In women, smoking raised breast cancer mortality, with a relative risk of 1.3. This association was strongly dose dependent. In men, smoking raised prostate cancer mortality, with a relative risk of 1.4.

This study was limited in that most of the participants were white and better educated than the general population, which may affect the applicability of the results to other populations.

Smoking causes death from many diseases that until now have not been linked officially to tobacco use, including digestive disorders, liver cirrhosis, infections, renal failure, and breast and prostate cancers, according to a report published online Feb. 11 in the New England Journal of Medicine.

“Our results suggest that the number of persons in the United States who die each year as a result of smoking cigarettes may be substantially greater than currently estimated,” said Brian D. Carter of the epidemiology research program, American Cancer Society, Atlanta, and his associates.

The 2014 Surgeon General’s report estimated that smoking causes more than 480,000 deaths every year in the United States, based on mortality figures from 21 diseases that have been formally established as caused by smoking: 12 types of cancer, 6 types of cardiovascular disease, diabetes, chronic obstructive pulmonary disease, and pneumonia. Mr. Carter and his associates pooled data from five large cohort studies to examine possible associations between smoking and an additional 31 cause-of-death categories. They now estimate that an additional 60,000-120,000 deaths each year can be attributed to smoking.

For their study, the investigators assessed 421,378 men and 532,651 women aged 55 years and older at baseline whose smoking status was carefully recorded and who were followed from 2000 to 2011 in the Cancer Prevention Study II Nutrition Cohort, the Nurses’ Health Study I, the Health Professionals Follow-up Study, the Women’s Health Initiative, and the National Institutes of Health-AARP Diet and Health Study.

As expected, smokers had a twofold to threefold higher mortality from any cause, compared with nonsmokers. Smokers also had a markedly higher risk of death than nonsmokers from all 21 causes already established as attributable to tobacco use, such as lung cancer, oral cancer, ischemic heart disease, atherosclerosis, and stroke. But approximately 17% of smokers’ excess mortality was accounted for by several diseases that previously have not been attributable to tobacco use.

For example, the risk of death due to intestinal ischemia was approximately six times higher among smokers than among nonsmokers, a remarkably strong association that was also reported in the Million Women Study. “Smoking acutely reduces blood flow to the intestines, and evidence suggests that smoking causes risk factors that can often lead to intestinal ischemia, including atherosclerosis, platelet aggregation, and congestive heart failure,” Mr. Carter and his associates said (N. Engl. J. Med. 2015 Feb. 12 [doi:10.1056/NEJMsa140721]).  In this study, smoking also more than doubled the risk of dying from other digestive diseases. Previous studies have suggested a link between smoking and digestive disorders such as Crohn’s disease, peptic ulcers, acute pancreatitis, paralytic ileus, bowel obstruction, choletlithiasis, diverticulitis, and gastrointestinal hemorrhage. “Although these diseases are not common causes of death, they account for millions of hospitalizations each year,” the investigators noted.

Continue for mortality risks >>

The mortality risk from liver cirrhosis, after the data were adjusted to account for alcohol consumption, was more than three times higher in smokers than in nonsmokers. Even smokers who did not drink alcohol were at significantly increased risk of cirrhosis, compared with nonsmokers.

The risk of death due to infection was 2.3 times higher in smokers than in nonsmokers. This strong association was dose-dependent, as infection-related mortality rose with increasing smoking intensity. And among study participants who had quit smoking, infection-related mortality declined as the number of years since cessation increased.

The rate of death due to renal failure was twice as high among smokers as among nonsmokers. And the rate of death due to hypertensive heart disease, the only category of heart disease not already established as smoking related, was 2.4 times higher in smokers. The latter association “is relevant for assessing the public health burden of smoking, since a considerable number of deaths in the United States are attributable to hypertensive heart disease,” according to Mr. Carter and his associates.

Smoking also was strongly associated with “multiple diseases too uncommon to examine individually.” This included all rare cancers combined, rare digestive diseases, and respiratory diseases other than those already known to stem from smoking.

In women, smoking raised breast cancer mortality, with a relative risk of 1.3. This association was strongly dose dependent. In men, smoking raised prostate cancer mortality, with a relative risk of 1.4.

This study was limited in that most of the participants were white and better educated than the general population, which may affect the applicability of the results to other populations.

Smoking causes death from many diseases that until now have not been linked officially to tobacco use, including digestive disorders, liver cirrhosis, infections, renal failure, and breast and prostate cancers, according to a report published online Feb. 11 in the New England Journal of Medicine.

“Our results suggest that the number of persons in the United States who die each year as a result of smoking cigarettes may be substantially greater than currently estimated,” said Brian D. Carter of the epidemiology research program, American Cancer Society, Atlanta, and his associates.

The 2014 Surgeon General’s report estimated that smoking causes more than 480,000 deaths every year in the United States, based on mortality figures from 21 diseases that have been formally established as caused by smoking: 12 types of cancer, 6 types of cardiovascular disease, diabetes, chronic obstructive pulmonary disease, and pneumonia. Mr. Carter and his associates pooled data from five large cohort studies to examine possible associations between smoking and an additional 31 cause-of-death categories. They now estimate that an additional 60,000-120,000 deaths each year can be attributed to smoking.

For their study, the investigators assessed 421,378 men and 532,651 women aged 55 years and older at baseline whose smoking status was carefully recorded and who were followed from 2000 to 2011 in the Cancer Prevention Study II Nutrition Cohort, the Nurses’ Health Study I, the Health Professionals Follow-up Study, the Women’s Health Initiative, and the National Institutes of Health-AARP Diet and Health Study.

As expected, smokers had a twofold to threefold higher mortality from any cause, compared with nonsmokers. Smokers also had a markedly higher risk of death than nonsmokers from all 21 causes already established as attributable to tobacco use, such as lung cancer, oral cancer, ischemic heart disease, atherosclerosis, and stroke. But approximately 17% of smokers’ excess mortality was accounted for by several diseases that previously have not been attributable to tobacco use.

For example, the risk of death due to intestinal ischemia was approximately six times higher among smokers than among nonsmokers, a remarkably strong association that was also reported in the Million Women Study. “Smoking acutely reduces blood flow to the intestines, and evidence suggests that smoking causes risk factors that can often lead to intestinal ischemia, including atherosclerosis, platelet aggregation, and congestive heart failure,” Mr. Carter and his associates said (N. Engl. J. Med. 2015 Feb. 12 [doi:10.1056/NEJMsa140721]).  In this study, smoking also more than doubled the risk of dying from other digestive diseases. Previous studies have suggested a link between smoking and digestive disorders such as Crohn’s disease, peptic ulcers, acute pancreatitis, paralytic ileus, bowel obstruction, choletlithiasis, diverticulitis, and gastrointestinal hemorrhage. “Although these diseases are not common causes of death, they account for millions of hospitalizations each year,” the investigators noted.

The mortality risk from liver cirrhosis, after the data were adjusted to account for alcohol consumption, was more than three times higher in smokers than in nonsmokers. Even smokers who did not drink alcohol were at significantly increased risk of cirrhosis, compared with nonsmokers.

The risk of death due to infection was 2.3 times higher in smokers than in nonsmokers. This strong association was dose-dependent, as infection-related mortality rose with increasing smoking intensity. And among study participants who had quit smoking, infection-related mortality declined as the number of years since cessation increased.

The rate of death due to renal failure was twice as high among smokers as among nonsmokers. And the rate of death due to hypertensive heart disease, the only category of heart disease not already established as smoking related, was 2.4 times higher in smokers. The latter association “is relevant for assessing the public health burden of smoking, since a considerable number of deaths in the United States are attributable to hypertensive heart disease,” according to Mr. Carter and his associates.

Smoking also was strongly associated with “multiple diseases too uncommon to examine individually.” This included all rare cancers combined, rare digestive diseases, and respiratory diseases other than those already known to stem from smoking.

In women, smoking raised breast cancer mortality, with a relative risk of 1.3. This association was strongly dose dependent. In men, smoking raised prostate cancer mortality, with a relative risk of 1.4.

This study was limited in that most of the participants were white and better educated than the general population, which may affect the applicability of the results to other populations.

Smoking causes death from many diseases that until now have not been linked officially to tobacco use, including digestive disorders, liver cirrhosis, infections, renal failure, and breast and prostate cancers, according to a report published online Feb. 11 in the New England Journal of Medicine.

“Our results suggest that the number of persons in the United States who die each year as a result of smoking cigarettes may be substantially greater than currently estimated,” said Brian D. Carter of the epidemiology research program, American Cancer Society, Atlanta, and his associates.

The 2014 Surgeon General’s report estimated that smoking causes more than 480,000 deaths every year in the United States, based on mortality figures from 21 diseases that have been formally established as caused by smoking: 12 types of cancer, 6 types of cardiovascular disease, diabetes, chronic obstructive pulmonary disease, and pneumonia. Mr. Carter and his associates pooled data from five large cohort studies to examine possible associations between smoking and an additional 31 cause-of-death categories. They now estimate that an additional 60,000-120,000 deaths each year can be attributed to smoking.

For their study, the investigators assessed 421,378 men and 532,651 women aged 55 years and older at baseline whose smoking status was carefully recorded and who were followed from 2000 to 2011 in the Cancer Prevention Study II Nutrition Cohort, the Nurses’ Health Study I, the Health Professionals Follow-up Study, the Women’s Health Initiative, and the National Institutes of Health-AARP Diet and Health Study.

As expected, smokers had a twofold to threefold higher mortality from any cause, compared with nonsmokers. Smokers also had a markedly higher risk of death than nonsmokers from all 21 causes already established as attributable to tobacco use, such as lung cancer, oral cancer, ischemic heart disease, atherosclerosis, and stroke. But approximately 17% of smokers’ excess mortality was accounted for by several diseases that previously have not been attributable to tobacco use.

For example, the risk of death due to intestinal ischemia was approximately six times higher among smokers than among nonsmokers, a remarkably strong association that was also reported in the Million Women Study. “Smoking acutely reduces blood flow to the intestines, and evidence suggests that smoking causes risk factors that can often lead to intestinal ischemia, including atherosclerosis, platelet aggregation, and congestive heart failure,” Mr. Carter and his associates said (N. Engl. J. Med. 2015 Feb. 12 [doi:10.1056/NEJMsa140721]).  In this study, smoking also more than doubled the risk of dying from other digestive diseases. Previous studies have suggested a link between smoking and digestive disorders such as Crohn’s disease, peptic ulcers, acute pancreatitis, paralytic ileus, bowel obstruction, choletlithiasis, diverticulitis, and gastrointestinal hemorrhage. “Although these diseases are not common causes of death, they account for millions of hospitalizations each year,” the investigators noted.

The mortality risk from liver cirrhosis, after the data were adjusted to account for alcohol consumption, was more than three times higher in smokers than in nonsmokers. Even smokers who did not drink alcohol were at significantly increased risk of cirrhosis, compared with nonsmokers.

The risk of death due to infection was 2.3 times higher in smokers than in nonsmokers. This strong association was dose-dependent, as infection-related mortality rose with increasing smoking intensity. And among study participants who had quit smoking, infection-related mortality declined as the number of years since cessation increased.

The rate of death due to renal failure was twice as high among smokers as among nonsmokers. And the rate of death due to hypertensive heart disease, the only category of heart disease not already established as smoking related, was 2.4 times higher in smokers. The latter association “is relevant for assessing the public health burden of smoking, since a considerable number of deaths in the United States are attributable to hypertensive heart disease,” according to Mr. Carter and his associates.

Smoking also was strongly associated with “multiple diseases too uncommon to examine individually.” This included all rare cancers combined, rare digestive diseases, and respiratory diseases other than those already known to stem from smoking.

In women, smoking raised breast cancer mortality, with a relative risk of 1.3. This association was strongly dose dependent. In men, smoking raised prostate cancer mortality, with a relative risk of 1.4.

This study was limited in that most of the participants were white and better educated than the general population, which may affect the applicability of the results to other populations.

Smoking causes death from many diseases that until now have not been linked officially to tobacco use, including digestive disorders, liver cirrhosis, infections, renal failure, and breast and prostate cancers, according to a report published online Feb. 11 in the New England Journal of Medicine.

“Our results suggest that the number of persons in the United States who die each year as a result of smoking cigarettes may be substantially greater than currently estimated,” said Brian D. Carter of the epidemiology research program, American Cancer Society, Atlanta, and his associates.

The 2014 Surgeon General’s report estimated that smoking causes more than 480,000 deaths every year in the United States, based on mortality figures from 21 diseases that have been formally established as caused by smoking: 12 types of cancer, 6 types of cardiovascular disease, diabetes, chronic obstructive pulmonary disease, and pneumonia. Mr. Carter and his associates pooled data from five large cohort studies to examine possible associations between smoking and an additional 31 cause-of-death categories. They now estimate that an additional 60,000-120,000 deaths each year can be attributed to smoking.

For their study, the investigators assessed 421,378 men and 532,651 women aged 55 years and older at baseline whose smoking status was carefully recorded and who were followed from 2000 to 2011 in the Cancer Prevention Study II Nutrition Cohort, the Nurses’ Health Study I, the Health Professionals Follow-up Study, the Women’s Health Initiative, and the National Institutes of Health-AARP Diet and Health Study.

As expected, smokers had a twofold to threefold higher mortality from any cause, compared with nonsmokers. Smokers also had a markedly higher risk of death than nonsmokers from all 21 causes already established as attributable to tobacco use, such as lung cancer, oral cancer, ischemic heart disease, atherosclerosis, and stroke. But approximately 17% of smokers’ excess mortality was accounted for by several diseases that previously have not been attributable to tobacco use.

For example, the risk of death due to intestinal ischemia was approximately six times higher among smokers than among nonsmokers, a remarkably strong association that was also reported in the Million Women Study. “Smoking acutely reduces blood flow to the intestines, and evidence suggests that smoking causes risk factors that can often lead to intestinal ischemia, including atherosclerosis, platelet aggregation, and congestive heart failure,” Mr. Carter and his associates said (N. Engl. J. Med. 2015 Feb. 12 [doi:10.1056/NEJMsa140721]).  In this study, smoking also more than doubled the risk of dying from other digestive diseases. Previous studies have suggested a link between smoking and digestive disorders such as Crohn’s disease, peptic ulcers, acute pancreatitis, paralytic ileus, bowel obstruction, choletlithiasis, diverticulitis, and gastrointestinal hemorrhage. “Although these diseases are not common causes of death, they account for millions of hospitalizations each year,” the investigators noted.

The mortality risk from liver cirrhosis, after the data were adjusted to account for alcohol consumption, was more than three times higher in smokers than in nonsmokers. Even smokers who did not drink alcohol were at significantly increased risk of cirrhosis, compared with nonsmokers.

The risk of death due to infection was 2.3 times higher in smokers than in nonsmokers. This strong association was dose-dependent, as infection-related mortality rose with increasing smoking intensity. And among study participants who had quit smoking, infection-related mortality declined as the number of years since cessation increased.

The rate of death due to renal failure was twice as high among smokers as among nonsmokers. And the rate of death due to hypertensive heart disease, the only category of heart disease not already established as smoking related, was 2.4 times higher in smokers. The latter association “is relevant for assessing the public health burden of smoking, since a considerable number of deaths in the United States are attributable to hypertensive heart disease,” according to Mr. Carter and his associates.

Smoking also was strongly associated with “multiple diseases too uncommon to examine individually.” This included all rare cancers combined, rare digestive diseases, and respiratory diseases other than those already known to stem from smoking.

In women, smoking raised breast cancer mortality, with a relative risk of 1.3. This association was strongly dose dependent. In men, smoking raised prostate cancer mortality, with a relative risk of 1.4.

This study was limited in that most of the participants were white and better educated than the general population, which may affect the applicability of the results to other populations.

The survival benefit conferred by implantable cardioverter-defibrillators (ICDs) persists with increasing patient age, but does attenuate, according to a report published online Feb.10 in Circulation: Cardiovascular Quality and Outcomes.

This indicates that “age per se should not be a contraindication to ICD placement. Rather, clinical judgment should take into account other factors, including patient preference, periprocedural risk, and comorbidity burden,” said Dr. Paul L. Hess of Duke Clinical Research Institute, Durham N.C., and his associates.

It is uncertain whether ICDs are effective at reducing sudden cardiac death in patients aged 75 years and older, largely because this age group has been underrepresented in clinical trials. Yet more than 40% of new ICDs are placed in older patients, including 10% placed in patients aged 80 years and older. Dr. Hess and his colleagues pooled data from five major clinical trials of ICDs to increase the sample size of older patients, allowing better appraisal of treatment effects in this age group. They retrospectively assessed survival outcomes in 3,530 patients who participated in the MADIT-I, MUSTT, MADIT-II, DEFINITE, and SCD-HeFT studies conducted in the United States, Canada, Italy, Germany, the Netherlands, and Israel.

The median age in this pooled sample was 62 years. There were 390 patients (11%) aged 75 years and older. Median follow-up after ICD placement was 2.6 years.

The primary outcome of interest – all-cause mortality – was 21.3% among ICD recipients, compared with 30.6% in patients who didn’t receive ICDs. “After adjusting for patient demographics, medical comorbidities, and laboratory values, point estimates indicated that the survival benefit of ICD therapy persists across the age spectrum,” the investigators said (Circ. Cardiovasc. Qual. Outcomes 2015 Feb. 10; [doi:10.1161/circoutcomes.114.001306]).

The survival benefit attenuated with increasing patient age. This may be because of an increase in competing causes of death as patients aged. However, the total number of participants aged 75 years and older was “modest” despite the pooling of data, “and this may have affected the corresponding efficacy estimates and the observed attenuation of ICD survival benefit,” Dr. Hess and his associates wrote.

The study also found no evidence that age influences the risk of rehospitalization after ICD placement.

The survival benefit conferred by implantable cardioverter-defibrillators (ICDs) persists with increasing patient age, but does attenuate, according to a report published online Feb.10 in Circulation: Cardiovascular Quality and Outcomes.

This indicates that “age per se should not be a contraindication to ICD placement. Rather, clinical judgment should take into account other factors, including patient preference, periprocedural risk, and comorbidity burden,” said Dr. Paul L. Hess of Duke Clinical Research Institute, Durham N.C., and his associates.

It is uncertain whether ICDs are effective at reducing sudden cardiac death in patients aged 75 years and older, largely because this age group has been underrepresented in clinical trials. Yet more than 40% of new ICDs are placed in older patients, including 10% placed in patients aged 80 years and older. Dr. Hess and his colleagues pooled data from five major clinical trials of ICDs to increase the sample size of older patients, allowing better appraisal of treatment effects in this age group. They retrospectively assessed survival outcomes in 3,530 patients who participated in the MADIT-I, MUSTT, MADIT-II, DEFINITE, and SCD-HeFT studies conducted in the United States, Canada, Italy, Germany, the Netherlands, and Israel.

The median age in this pooled sample was 62 years. There were 390 patients (11%) aged 75 years and older. Median follow-up after ICD placement was 2.6 years.

The primary outcome of interest – all-cause mortality – was 21.3% among ICD recipients, compared with 30.6% in patients who didn’t receive ICDs. “After adjusting for patient demographics, medical comorbidities, and laboratory values, point estimates indicated that the survival benefit of ICD therapy persists across the age spectrum,” the investigators said (Circ. Cardiovasc. Qual. Outcomes 2015 Feb. 10; [doi:10.1161/circoutcomes.114.001306]).

The survival benefit attenuated with increasing patient age. This may be because of an increase in competing causes of death as patients aged. However, the total number of participants aged 75 years and older was “modest” despite the pooling of data, “and this may have affected the corresponding efficacy estimates and the observed attenuation of ICD survival benefit,” Dr. Hess and his associates wrote.

The study also found no evidence that age influences the risk of rehospitalization after ICD placement.

The survival benefit conferred by implantable cardioverter-defibrillators (ICDs) persists with increasing patient age, but does attenuate, according to a report published online Feb.10 in Circulation: Cardiovascular Quality and Outcomes.

This indicates that “age per se should not be a contraindication to ICD placement. Rather, clinical judgment should take into account other factors, including patient preference, periprocedural risk, and comorbidity burden,” said Dr. Paul L. Hess of Duke Clinical Research Institute, Durham N.C., and his associates.

It is uncertain whether ICDs are effective at reducing sudden cardiac death in patients aged 75 years and older, largely because this age group has been underrepresented in clinical trials. Yet more than 40% of new ICDs are placed in older patients, including 10% placed in patients aged 80 years and older. Dr. Hess and his colleagues pooled data from five major clinical trials of ICDs to increase the sample size of older patients, allowing better appraisal of treatment effects in this age group. They retrospectively assessed survival outcomes in 3,530 patients who participated in the MADIT-I, MUSTT, MADIT-II, DEFINITE, and SCD-HeFT studies conducted in the United States, Canada, Italy, Germany, the Netherlands, and Israel.

The median age in this pooled sample was 62 years. There were 390 patients (11%) aged 75 years and older. Median follow-up after ICD placement was 2.6 years.

The primary outcome of interest – all-cause mortality – was 21.3% among ICD recipients, compared with 30.6% in patients who didn’t receive ICDs. “After adjusting for patient demographics, medical comorbidities, and laboratory values, point estimates indicated that the survival benefit of ICD therapy persists across the age spectrum,” the investigators said (Circ. Cardiovasc. Qual. Outcomes 2015 Feb. 10; [doi:10.1161/circoutcomes.114.001306]).

The survival benefit attenuated with increasing patient age. This may be because of an increase in competing causes of death as patients aged. However, the total number of participants aged 75 years and older was “modest” despite the pooling of data, “and this may have affected the corresponding efficacy estimates and the observed attenuation of ICD survival benefit,” Dr. Hess and his associates wrote.

The study also found no evidence that age influences the risk of rehospitalization after ICD placement.

Crizotinib was strikingly effective, inducing an 80% response rate, against refractory stage 4 non–small-cell lung adenocarcinoma expressing rearrangements of the c-ros oncogene 1 (ROS1) in a small retrospective cohort study.

The results were published online Feb. 9 in Journal of Clinical Oncology.

This suggests that all patients with lung adenocarcinoma should be screened for ROS1 to allow targeted therapy, much as they are currently screened for EGFR, ALK, and KRAS mutations, said Dr. Julien Mazieres of the thoracic oncology unit, Hopital Larrey, Centre Hospitalier Universitaire Toulouse, France, and his associates.

ROS1 encodes a tyrosine kinase receptor. Crizotinib is an oral tyrosine kinase inhibitor approved for use in advanced lung cancers that have ALK rearrangement or MET amplification. Recent preclinical and phase I studies indicate that the drug also shows “impressive clinical activity” against ROS1-positive lung cancers, “with striking results reported in individual patients,” Dr. Mazieres and his colleagues said.

To characterize the experience to date with crizotinib in this patient population, the researchers assessed the outcomes of all 31 consecutive patients with stage 4 NSCLC carrying ROS1 rearrangements who have been treated with off-label crizotinib at 16 European cancer centers that currently screen for ROS1. In contrast to the typical profile of people with lung cancer, these patients tended to be younger (median age, 50 years), nonsmoking, and female. All but one had already received at least one line of chemotherapy, and most had progressive disease despite receiving two or more lines.

A total of 24 of the 31 patients showed objective responses to crizotinib, including 5 who showed complete responses; 4 patients showed disease progression despite crizotinib. This yielded an overall response rate of 80% and a disease control rate of 86%. The median progression-free survival was 9.1 months. The rate of progression-free survival at 1 year was 44%, the investigators said (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.58.3302]).

These findings confirm the 72% overall response rate reported in a recently published phase I clinical trial involving similar patients. “Thus, we have shown that the findings reported in highly selected patients in a phase I trial can be translated into the routine use of a drug,” Dr. Mazieres and his associates said.

The patient records documented severe (grade 4 or 5) toxicities, and none occurred in this series of patients. No patients discontinued crizotinib because of adverse effects.

The incidence of ROS1 rearrangements in NSCLCs is low, estimated to occur in 2% or fewer of unselected adenocarcinomas. Nevertheless, “we believe that targeted therapies with response rates of more than 50% represent a major breakthrough in lung cancer therapy and should be a priority in drug development,” the researchers said.

At present there are several methods available to test for ROS1, but the best method has not yet been identified, they added.

Crizotinib was strikingly effective, inducing an 80% response rate, against refractory stage 4 non–small-cell lung adenocarcinoma expressing rearrangements of the c-ros oncogene 1 (ROS1) in a small retrospective cohort study.

The results were published online Feb. 9 in Journal of Clinical Oncology.

This suggests that all patients with lung adenocarcinoma should be screened for ROS1 to allow targeted therapy, much as they are currently screened for EGFR, ALK, and KRAS mutations, said Dr. Julien Mazieres of the thoracic oncology unit, Hopital Larrey, Centre Hospitalier Universitaire Toulouse, France, and his associates.

ROS1 encodes a tyrosine kinase receptor. Crizotinib is an oral tyrosine kinase inhibitor approved for use in advanced lung cancers that have ALK rearrangement or MET amplification. Recent preclinical and phase I studies indicate that the drug also shows “impressive clinical activity” against ROS1-positive lung cancers, “with striking results reported in individual patients,” Dr. Mazieres and his colleagues said.

To characterize the experience to date with crizotinib in this patient population, the researchers assessed the outcomes of all 31 consecutive patients with stage 4 NSCLC carrying ROS1 rearrangements who have been treated with off-label crizotinib at 16 European cancer centers that currently screen for ROS1. In contrast to the typical profile of people with lung cancer, these patients tended to be younger (median age, 50 years), nonsmoking, and female. All but one had already received at least one line of chemotherapy, and most had progressive disease despite receiving two or more lines.

A total of 24 of the 31 patients showed objective responses to crizotinib, including 5 who showed complete responses; 4 patients showed disease progression despite crizotinib. This yielded an overall response rate of 80% and a disease control rate of 86%. The median progression-free survival was 9.1 months. The rate of progression-free survival at 1 year was 44%, the investigators said (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.58.3302]).

These findings confirm the 72% overall response rate reported in a recently published phase I clinical trial involving similar patients. “Thus, we have shown that the findings reported in highly selected patients in a phase I trial can be translated into the routine use of a drug,” Dr. Mazieres and his associates said.

The patient records documented severe (grade 4 or 5) toxicities, and none occurred in this series of patients. No patients discontinued crizotinib because of adverse effects.

The incidence of ROS1 rearrangements in NSCLCs is low, estimated to occur in 2% or fewer of unselected adenocarcinomas. Nevertheless, “we believe that targeted therapies with response rates of more than 50% represent a major breakthrough in lung cancer therapy and should be a priority in drug development,” the researchers said.

At present there are several methods available to test for ROS1, but the best method has not yet been identified, they added.

Crizotinib was strikingly effective, inducing an 80% response rate, against refractory stage 4 non–small-cell lung adenocarcinoma expressing rearrangements of the c-ros oncogene 1 (ROS1) in a small retrospective cohort study.

The results were published online Feb. 9 in Journal of Clinical Oncology.

This suggests that all patients with lung adenocarcinoma should be screened for ROS1 to allow targeted therapy, much as they are currently screened for EGFR, ALK, and KRAS mutations, said Dr. Julien Mazieres of the thoracic oncology unit, Hopital Larrey, Centre Hospitalier Universitaire Toulouse, France, and his associates.

ROS1 encodes a tyrosine kinase receptor. Crizotinib is an oral tyrosine kinase inhibitor approved for use in advanced lung cancers that have ALK rearrangement or MET amplification. Recent preclinical and phase I studies indicate that the drug also shows “impressive clinical activity” against ROS1-positive lung cancers, “with striking results reported in individual patients,” Dr. Mazieres and his colleagues said.

To characterize the experience to date with crizotinib in this patient population, the researchers assessed the outcomes of all 31 consecutive patients with stage 4 NSCLC carrying ROS1 rearrangements who have been treated with off-label crizotinib at 16 European cancer centers that currently screen for ROS1. In contrast to the typical profile of people with lung cancer, these patients tended to be younger (median age, 50 years), nonsmoking, and female. All but one had already received at least one line of chemotherapy, and most had progressive disease despite receiving two or more lines.

A total of 24 of the 31 patients showed objective responses to crizotinib, including 5 who showed complete responses; 4 patients showed disease progression despite crizotinib. This yielded an overall response rate of 80% and a disease control rate of 86%. The median progression-free survival was 9.1 months. The rate of progression-free survival at 1 year was 44%, the investigators said (J. Clin. Oncol. 2015 Feb. 9 [doi:10.1200/JCO.2014.58.3302]).

These findings confirm the 72% overall response rate reported in a recently published phase I clinical trial involving similar patients. “Thus, we have shown that the findings reported in highly selected patients in a phase I trial can be translated into the routine use of a drug,” Dr. Mazieres and his associates said.

The patient records documented severe (grade 4 or 5) toxicities, and none occurred in this series of patients. No patients discontinued crizotinib because of adverse effects.

The incidence of ROS1 rearrangements in NSCLCs is low, estimated to occur in 2% or fewer of unselected adenocarcinomas. Nevertheless, “we believe that targeted therapies with response rates of more than 50% represent a major breakthrough in lung cancer therapy and should be a priority in drug development,” the researchers said.

At present there are several methods available to test for ROS1, but the best method has not yet been identified, they added.

For patients who have active multiple sclerosis despite using injectable immunomodulators, switching to the oral immunomodulator fingolimod yields fewer relapses and less disability than did switching to a different injectable immunomodulator, according to a report published online Feb. 9 in JAMA Neurology.

To compare MS outcomes using different treatment regimens, researchers used information from the MSBase registry, which collects observational data on the disorder as part of routine patient care. For this study, the investigators retrospectively analyzed data entered during 1996-2014 for 527 patients who had breakthrough disease while receiving injectable immunomodulators (typically an interferon beta/glatiramer acetate preparation) and who switched to either oral fingolimod (148 patients) or a different interferon beta/glatiramer agent (379 patients).

©solitude72/iStockphoto

The two groups were propensity matched for baseline clinical and demographic variables, including patient age, area of residence, MS duration, total number of previous treatments, disability score, number of relapses, and previous medications. They were followed for a median of 13 months (range, 3-80 months) after switching therapies, said Dr. Anna He of the department of neurology, Royal Melbourne Hospital, and her associates.

Patients who switched to fingolimod showed a decreased risk of relapse, compared with patients who switched to a different injectable, with a hazard ratio of 0.74. They also showed a 47% decreased risk of progression of disability (HR, 0.53). And the fingolimod group showed a markedly increased likelihood of disability regression (HR, 2.0). In addition, the rate of continuing on the new treatment at 2 years was higher with fingolimod (82.5%) than with a different injectable (73.2%), Dr. He and her associates said (JAMA Neurol. 2015 Feb. 9 [doi:10.1001/jamaneurol.2014.4147]).

“Although analyses of observational data do not serve as a substitute for trial data, our study provides real-world evidence, representative of clinical practice in tertiary MS centers, to support clinical decision-making that is highly relevant to the management of active MS,” the investigators said.

This study was supported by Novartis, the maker of fingolimod; Multiple Sclerosis Research Australia; the Australian National Health and Medical Research Council; the Centre for Research Excellence; and the MSBase Foundation, a not-for-profit group that receives support from Bayer Schering, Biogen Idec, Merck Serono, Novartis, and Sanofi. Dr. He reported having no financial disclosures; her associates reported ties to numerous industry sources.

For patients who have active multiple sclerosis despite using injectable immunomodulators, switching to the oral immunomodulator fingolimod yields fewer relapses and less disability than did switching to a different injectable immunomodulator, according to a report published online Feb. 9 in JAMA Neurology.

To compare MS outcomes using different treatment regimens, researchers used information from the MSBase registry, which collects observational data on the disorder as part of routine patient care. For this study, the investigators retrospectively analyzed data entered during 1996-2014 for 527 patients who had breakthrough disease while receiving injectable immunomodulators (typically an interferon beta/glatiramer acetate preparation) and who switched to either oral fingolimod (148 patients) or a different interferon beta/glatiramer agent (379 patients).

©solitude72/iStockphoto

The two groups were propensity matched for baseline clinical and demographic variables, including patient age, area of residence, MS duration, total number of previous treatments, disability score, number of relapses, and previous medications. They were followed for a median of 13 months (range, 3-80 months) after switching therapies, said Dr. Anna He of the department of neurology, Royal Melbourne Hospital, and her associates.

Patients who switched to fingolimod showed a decreased risk of relapse, compared with patients who switched to a different injectable, with a hazard ratio of 0.74. They also showed a 47% decreased risk of progression of disability (HR, 0.53). And the fingolimod group showed a markedly increased likelihood of disability regression (HR, 2.0). In addition, the rate of continuing on the new treatment at 2 years was higher with fingolimod (82.5%) than with a different injectable (73.2%), Dr. He and her associates said (JAMA Neurol. 2015 Feb. 9 [doi:10.1001/jamaneurol.2014.4147]).

“Although analyses of observational data do not serve as a substitute for trial data, our study provides real-world evidence, representative of clinical practice in tertiary MS centers, to support clinical decision-making that is highly relevant to the management of active MS,” the investigators said.

This study was supported by Novartis, the maker of fingolimod; Multiple Sclerosis Research Australia; the Australian National Health and Medical Research Council; the Centre for Research Excellence; and the MSBase Foundation, a not-for-profit group that receives support from Bayer Schering, Biogen Idec, Merck Serono, Novartis, and Sanofi. Dr. He reported having no financial disclosures; her associates reported ties to numerous industry sources.

For patients who have active multiple sclerosis despite using injectable immunomodulators, switching to the oral immunomodulator fingolimod yields fewer relapses and less disability than did switching to a different injectable immunomodulator, according to a report published online Feb. 9 in JAMA Neurology.

To compare MS outcomes using different treatment regimens, researchers used information from the MSBase registry, which collects observational data on the disorder as part of routine patient care. For this study, the investigators retrospectively analyzed data entered during 1996-2014 for 527 patients who had breakthrough disease while receiving injectable immunomodulators (typically an interferon beta/glatiramer acetate preparation) and who switched to either oral fingolimod (148 patients) or a different interferon beta/glatiramer agent (379 patients).

©solitude72/iStockphoto

The two groups were propensity matched for baseline clinical and demographic variables, including patient age, area of residence, MS duration, total number of previous treatments, disability score, number of relapses, and previous medications. They were followed for a median of 13 months (range, 3-80 months) after switching therapies, said Dr. Anna He of the department of neurology, Royal Melbourne Hospital, and her associates.

Patients who switched to fingolimod showed a decreased risk of relapse, compared with patients who switched to a different injectable, with a hazard ratio of 0.74. They also showed a 47% decreased risk of progression of disability (HR, 0.53). And the fingolimod group showed a markedly increased likelihood of disability regression (HR, 2.0). In addition, the rate of continuing on the new treatment at 2 years was higher with fingolimod (82.5%) than with a different injectable (73.2%), Dr. He and her associates said (JAMA Neurol. 2015 Feb. 9 [doi:10.1001/jamaneurol.2014.4147]).

“Although analyses of observational data do not serve as a substitute for trial data, our study provides real-world evidence, representative of clinical practice in tertiary MS centers, to support clinical decision-making that is highly relevant to the management of active MS,” the investigators said.

This study was supported by Novartis, the maker of fingolimod; Multiple Sclerosis Research Australia; the Australian National Health and Medical Research Council; the Centre for Research Excellence; and the MSBase Foundation, a not-for-profit group that receives support from Bayer Schering, Biogen Idec, Merck Serono, Novartis, and Sanofi. Dr. He reported having no financial disclosures; her associates reported ties to numerous industry sources.

A new endoluminal device that reduces the coronary sinus significantly improved refractory angina in patients with advanced coronary artery disease who weren’t candidates for revascularization in a small phase II clinical trial. The results were published online Feb. 5 in the New England Journal of Medicine.

The international, randomized, double-blind study, sponsored by Neovasc, maker of the Reducer device, involved 104 patients enrolled who had Canadian Cardiovascular Society (CCS) class III or IV angina despite maximal medical therapy, evidence of reversible myocardial ischemia, and a left ventricular ejection fraction over 25%. These participants (mean age 68 years; range, 35-87 years) underwent right heart catheterization with angiography of the coronary sinus to determine whether the anatomy was suitable for implantation. Then 52 underwent implantation (the treatment group) and 52 underwent a sham procedure (the control group), and all were followed for up to 3 years, said Dr. Stefan Verheye of Antwerp (Belgium) Cardiovascular Center and his associates.

Courtesy Neovasc Inc.

The stainless steel device is balloon expandable and shaped like an hourglass. It creates a focal narrowing that increases pressure in the coronary sinus, which is thought to recruit coronary collateral blood flow, redistributing blood from the less-ischemic epicardium to the ischemic endocardium. The primary efficacy end point of the trial – the number of patients whose angina improved by two or more CCS classes within 6 months – was achieved by more than twice as many patients in the treatment group (18, or 35%) as in the control group (8, or 15%).

A total of 37 patients (71%) who received active treatment showed an improvement of at least one CCS class, compared with 22 (42%) of those who received the sham treatment. Quality of life, as measured by Seattle Angina Questionnaire score, improved by 17.6 out of a possible 100 points for active treatment, compared with 7.6 points for sham treatment. And exercise duration improved by 1 minute (13%) for active treatment, compared with 4 seconds (1%) for sham treatment, Dr. Verheye and his associates said (N. Engl. J. Med. 2015 Feb. 5 [doi:10.1056/NEJMoa1402556]). “Our study was not statistically powered to detect an improvement in ischemia by means of objective measures such as stress testing or wall-motion index. A larger trial would be necessary to show such a benefit,” they noted.

There were 76 adverse events in patients who received the implant and 93 in the control group; the numbers of serious adverse events in this high-risk cohort were 10 and 24, respectively. This included one periprocedural MI that occurred in a patient receiving active treatment. Among 36 of the patients who received the implant and later underwent CT angiography, none showed any evidence of device migration or occlusion, the investigators added.

This study was supported by Neovasc, manufacturer of the Reducer device. Dr. Verheye reported having no financial disclosures. His associates reported ties to Neovasc, Abbott, Boston Scientific, Novo Nordisk, Eli Lilly, and Zealand Pharma.

A new endoluminal device that reduces the coronary sinus significantly improved refractory angina in patients with advanced coronary artery disease who weren’t candidates for revascularization in a small phase II clinical trial. The results were published online Feb. 5 in the New England Journal of Medicine.

The international, randomized, double-blind study, sponsored by Neovasc, maker of the Reducer device, involved 104 patients enrolled who had Canadian Cardiovascular Society (CCS) class III or IV angina despite maximal medical therapy, evidence of reversible myocardial ischemia, and a left ventricular ejection fraction over 25%. These participants (mean age 68 years; range, 35-87 years) underwent right heart catheterization with angiography of the coronary sinus to determine whether the anatomy was suitable for implantation. Then 52 underwent implantation (the treatment group) and 52 underwent a sham procedure (the control group), and all were followed for up to 3 years, said Dr. Stefan Verheye of Antwerp (Belgium) Cardiovascular Center and his associates.

Courtesy Neovasc Inc.

The stainless steel device is balloon expandable and shaped like an hourglass. It creates a focal narrowing that increases pressure in the coronary sinus, which is thought to recruit coronary collateral blood flow, redistributing blood from the less-ischemic epicardium to the ischemic endocardium. The primary efficacy end point of the trial – the number of patients whose angina improved by two or more CCS classes within 6 months – was achieved by more than twice as many patients in the treatment group (18, or 35%) as in the control group (8, or 15%).

A total of 37 patients (71%) who received active treatment showed an improvement of at least one CCS class, compared with 22 (42%) of those who received the sham treatment. Quality of life, as measured by Seattle Angina Questionnaire score, improved by 17.6 out of a possible 100 points for active treatment, compared with 7.6 points for sham treatment. And exercise duration improved by 1 minute (13%) for active treatment, compared with 4 seconds (1%) for sham treatment, Dr. Verheye and his associates said (N. Engl. J. Med. 2015 Feb. 5 [doi:10.1056/NEJMoa1402556]). “Our study was not statistically powered to detect an improvement in ischemia by means of objective measures such as stress testing or wall-motion index. A larger trial would be necessary to show such a benefit,” they noted.

There were 76 adverse events in patients who received the implant and 93 in the control group; the numbers of serious adverse events in this high-risk cohort were 10 and 24, respectively. This included one periprocedural MI that occurred in a patient receiving active treatment. Among 36 of the patients who received the implant and later underwent CT angiography, none showed any evidence of device migration or occlusion, the investigators added.

This study was supported by Neovasc, manufacturer of the Reducer device. Dr. Verheye reported having no financial disclosures. His associates reported ties to Neovasc, Abbott, Boston Scientific, Novo Nordisk, Eli Lilly, and Zealand Pharma.

A new endoluminal device that reduces the coronary sinus significantly improved refractory angina in patients with advanced coronary artery disease who weren’t candidates for revascularization in a small phase II clinical trial. The results were published online Feb. 5 in the New England Journal of Medicine.

The international, randomized, double-blind study, sponsored by Neovasc, maker of the Reducer device, involved 104 patients enrolled who had Canadian Cardiovascular Society (CCS) class III or IV angina despite maximal medical therapy, evidence of reversible myocardial ischemia, and a left ventricular ejection fraction over 25%. These participants (mean age 68 years; range, 35-87 years) underwent right heart catheterization with angiography of the coronary sinus to determine whether the anatomy was suitable for implantation. Then 52 underwent implantation (the treatment group) and 52 underwent a sham procedure (the control group), and all were followed for up to 3 years, said Dr. Stefan Verheye of Antwerp (Belgium) Cardiovascular Center and his associates.

Courtesy Neovasc Inc.

The stainless steel device is balloon expandable and shaped like an hourglass. It creates a focal narrowing that increases pressure in the coronary sinus, which is thought to recruit coronary collateral blood flow, redistributing blood from the less-ischemic epicardium to the ischemic endocardium. The primary efficacy end point of the trial – the number of patients whose angina improved by two or more CCS classes within 6 months – was achieved by more than twice as many patients in the treatment group (18, or 35%) as in the control group (8, or 15%).

A total of 37 patients (71%) who received active treatment showed an improvement of at least one CCS class, compared with 22 (42%) of those who received the sham treatment. Quality of life, as measured by Seattle Angina Questionnaire score, improved by 17.6 out of a possible 100 points for active treatment, compared with 7.6 points for sham treatment. And exercise duration improved by 1 minute (13%) for active treatment, compared with 4 seconds (1%) for sham treatment, Dr. Verheye and his associates said (N. Engl. J. Med. 2015 Feb. 5 [doi:10.1056/NEJMoa1402556]). “Our study was not statistically powered to detect an improvement in ischemia by means of objective measures such as stress testing or wall-motion index. A larger trial would be necessary to show such a benefit,” they noted.

There were 76 adverse events in patients who received the implant and 93 in the control group; the numbers of serious adverse events in this high-risk cohort were 10 and 24, respectively. This included one periprocedural MI that occurred in a patient receiving active treatment. Among 36 of the patients who received the implant and later underwent CT angiography, none showed any evidence of device migration or occlusion, the investigators added.

This study was supported by Neovasc, manufacturer of the Reducer device. Dr. Verheye reported having no financial disclosures. His associates reported ties to Neovasc, Abbott, Boston Scientific, Novo Nordisk, Eli Lilly, and Zealand Pharma.

Hospitals participating in a monitoring and feedback program for surgical quality showed no more improvement in patient mortality, serious complications, reoperation, or readmission than hospitals not participating in the program, according to two separate reports published online Feb. 3 in JAMA.

Both research groups concluded that feedback on outcomes alone may not be sufficient to improve surgical outcomes.

The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) is an extensive clinical registry that provides participating hospitals with detailed descriptions of outcomes such as mortality, length of stay, and complications, allowing them to benchmark their performance relative to other participating hospitals and focus their efforts to improve care on the areas in which they perform poorly. The information is not reported publicly. Proponents contend that this targeting has already improved surgical outcomes as reported in several single-center studies, but others argue that any improvements noted so far might have occurred over time anyway.

©Daniel Mirer/thinkstockphotos.com

The best way to examine the question would be to compare outcomes between participating and nonparticipating hospitals, according to the two groups of investigators who did just that in these studies. However, the American College of Surgeons took issue with both study designs and released a statement taking exception to their approach to measuring surgical complications.

In the first study, researchers analyzed 30-day outcomes during a 10-year period at 263 hospitals participating in the ACS NSQIP and 526 nonparticipating propensity-matched hospitals across the United States. They focused on patients aged 65-99 years undergoing 11 high-risk general or vascular surgical procedures that are most in need of quality improvement: esophagectomy, pancreatic resection, colon resection, gastrectomy, liver resection, ventral hernia repair, cholecystectomy, appendectomy, abdominal aortic aneurysm repair, lower-extremity bypass, and carotid endarterectomy, said Dr. Nicholas H. Osborne of the Center for Healthcare Outcomes and Policy, University of Michigan, Ann Arbor, and a vascular surgeon at the university and his associates.

They found “slight trends toward improved outcomes” in NSQIP hospitals over time, but control hospitals showed the same trends. For example, 30-day mortality declined from 4.6% to 4.2% in participating hospitals during the study period, and similarly declined from 4.9% to 4.6% in nonparticipating hospitals. However, further analysis showed no statistically significant reductions after enrollment in the NSQIP in 30-day mortality, serious complications, reoperations, or readmissions, Dr. Osborne and his associates said (JAMA 2015 Feb. 3 [doi:10.1001/jama.2015.25]).

The underlying reasons for a lack of improvement among participating hospitals aren’t yet known, but it is possible that hospitals never implemented quality improvement efforts after being informed of their shortcomings, or that they implemented ineffective remedies. “Clinical quality improvement is challenging for hospitals. Changing physician practice requires complex, sustained, multifaceted interventions, and most hospitals may not have the expertise or resources to launch effective quality improvement interventions,” Dr. Osborne and his associates added.

In the second study, researchers analyzed surgical outcomes over a 4-year period among 113 academic hospitals in a health care system database; 39% of these hospitals participated in the NSQIP, receiving feedback on their performance, and the remaining 61% did not. This study evaluated 345,357 hospitalizations for 16 elective general and vascular surgeries, including many of the procedures covered in Dr. Osborne’s study plus mastectomy, thyroid procedures, open or laparoscopic colectomy, prostatectomy, and bariatric procedures, said Dr. David A. Etzioni, a surgeon at Mayo Clinic Arizona, Phoenix, and of the Kern Center for the Science of Health Care Delivery, and his associates.

This study also showed a slight decrease over time in postoperative complications, serious complications, and mortality at both NSQIP and non-NSQIP hospitals. “After accounting for patient risk, procedure type, underlying hospital performance, and temporal trends, the [statistical] model demonstrated no significant differences over time between NSQIP and non-NSQIP hospitals in terms of likelihood of complications, serious complications, or mortality,” Dr. Etzioni and his associates said (JAMA 2015 Feb. 3 [doi:10.1001/jama.2015.90]).

Their findings indicate that quality reports do not necessarily translate into evidence-based strategies for quality improvement and “suggest that a surgical outcomes reporting system does not provide a clear mechanism for quality improvement,” they noted.

In response to these reports, the American College of Surgeons released a statement emphasizing that claims data such as those used by both Osborne et al. and Etzioni et al. “are inaccurate and inappropriate for measuring surgical complications.” Furthermore, Dr. Clifford Ko, ACS director of the division of research and optimal patient care, called it “irresponsible to use data that are known to be an inaccurate measure of quality to determine the effectiveness of a quality improvement program.”

In addition, real-world experience shows that hospitals tend to focus on specific complications one at a time (such as surgical site infections) rather than amalgamating all complications. Hospitals also tend to address performance by separate specialties (such as urology) rather than on particular procedures (such as prostatectomy), according to the ACS statement.

Dr. Osborne’s study was supported in part by the National Institute on Aging. Dr. Osborne reported having no financial disclosures; one of his associates reported ties to Arbor Metrix. Dr. Etzioni’s study did not list any sources of financial support. Dr. Etzioni and his associates reported having no financial disclosures.

Hospitals participating in a monitoring and feedback program for surgical quality showed no more improvement in patient mortality, serious complications, reoperation, or readmission than hospitals not participating in the program, according to two separate reports published online Feb. 3 in JAMA.

Both research groups concluded that feedback on outcomes alone may not be sufficient to improve surgical outcomes.

The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) is an extensive clinical registry that provides participating hospitals with detailed descriptions of outcomes such as mortality, length of stay, and complications, allowing them to benchmark their performance relative to other participating hospitals and focus their efforts to improve care on the areas in which they perform poorly. The information is not reported publicly. Proponents contend that this targeting has already improved surgical outcomes as reported in several single-center studies, but others argue that any improvements noted so far might have occurred over time anyway.

©Daniel Mirer/thinkstockphotos.com

The best way to examine the question would be to compare outcomes between participating and nonparticipating hospitals, according to the two groups of investigators who did just that in these studies. However, the American College of Surgeons took issue with both study designs and released a statement taking exception to their approach to measuring surgical complications.

In the first study, researchers analyzed 30-day outcomes during a 10-year period at 263 hospitals participating in the ACS NSQIP and 526 nonparticipating propensity-matched hospitals across the United States. They focused on patients aged 65-99 years undergoing 11 high-risk general or vascular surgical procedures that are most in need of quality improvement: esophagectomy, pancreatic resection, colon resection, gastrectomy, liver resection, ventral hernia repair, cholecystectomy, appendectomy, abdominal aortic aneurysm repair, lower-extremity bypass, and carotid endarterectomy, said Dr. Nicholas H. Osborne of the Center for Healthcare Outcomes and Policy, University of Michigan, Ann Arbor, and a vascular surgeon at the university and his associates.

They found “slight trends toward improved outcomes” in NSQIP hospitals over time, but control hospitals showed the same trends. For example, 30-day mortality declined from 4.6% to 4.2% in participating hospitals during the study period, and similarly declined from 4.9% to 4.6% in nonparticipating hospitals. However, further analysis showed no statistically significant reductions after enrollment in the NSQIP in 30-day mortality, serious complications, reoperations, or readmissions, Dr. Osborne and his associates said (JAMA 2015 Feb. 3 [doi:10.1001/jama.2015.25]).

The underlying reasons for a lack of improvement among participating hospitals aren’t yet known, but it is possible that hospitals never implemented quality improvement efforts after being informed of their shortcomings, or that they implemented ineffective remedies. “Clinical quality improvement is challenging for hospitals. Changing physician practice requires complex, sustained, multifaceted interventions, and most hospitals may not have the expertise or resources to launch effective quality improvement interventions,” Dr. Osborne and his associates added.

In the second study, researchers analyzed surgical outcomes over a 4-year period among 113 academic hospitals in a health care system database; 39% of these hospitals participated in the NSQIP, receiving feedback on their performance, and the remaining 61% did not. This study evaluated 345,357 hospitalizations for 16 elective general and vascular surgeries, including many of the procedures covered in Dr. Osborne’s study plus mastectomy, thyroid procedures, open or laparoscopic colectomy, prostatectomy, and bariatric procedures, said Dr. David A. Etzioni, a surgeon at Mayo Clinic Arizona, Phoenix, and of the Kern Center for the Science of Health Care Delivery, and his associates.

This study also showed a slight decrease over time in postoperative complications, serious complications, and mortality at both NSQIP and non-NSQIP hospitals. “After accounting for patient risk, procedure type, underlying hospital performance, and temporal trends, the [statistical] model demonstrated no significant differences over time between NSQIP and non-NSQIP hospitals in terms of likelihood of complications, serious complications, or mortality,” Dr. Etzioni and his associates said (JAMA 2015 Feb. 3 [doi:10.1001/jama.2015.90]).

Their findings indicate that quality reports do not necessarily translate into evidence-based strategies for quality improvement and “suggest that a surgical outcomes reporting system does not provide a clear mechanism for quality improvement,” they noted.

In response to these reports, the American College of Surgeons released a statement emphasizing that claims data such as those used by both Osborne et al. and Etzioni et al. “are inaccurate and inappropriate for measuring surgical complications.” Furthermore, Dr. Clifford Ko, ACS director of the division of research and optimal patient care, called it “irresponsible to use data that are known to be an inaccurate measure of quality to determine the effectiveness of a quality improvement program.”

In addition, real-world experience shows that hospitals tend to focus on specific complications one at a time (such as surgical site infections) rather than amalgamating all complications. Hospitals also tend to address performance by separate specialties (such as urology) rather than on particular procedures (such as prostatectomy), according to the ACS statement.

Dr. Osborne’s study was supported in part by the National Institute on Aging. Dr. Osborne reported having no financial disclosures; one of his associates reported ties to Arbor Metrix. Dr. Etzioni’s study did not list any sources of financial support. Dr. Etzioni and his associates reported having no financial disclosures.

Hospitals participating in a monitoring and feedback program for surgical quality showed no more improvement in patient mortality, serious complications, reoperation, or readmission than hospitals not participating in the program, according to two separate reports published online Feb. 3 in JAMA.

Both research groups concluded that feedback on outcomes alone may not be sufficient to improve surgical outcomes.

The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) is an extensive clinical registry that provides participating hospitals with detailed descriptions of outcomes such as mortality, length of stay, and complications, allowing them to benchmark their performance relative to other participating hospitals and focus their efforts to improve care on the areas in which they perform poorly. The information is not reported publicly. Proponents contend that this targeting has already improved surgical outcomes as reported in several single-center studies, but others argue that any improvements noted so far might have occurred over time anyway.

©Daniel Mirer/thinkstockphotos.com

The best way to examine the question would be to compare outcomes between participating and nonparticipating hospitals, according to the two groups of investigators who did just that in these studies. However, the American College of Surgeons took issue with both study designs and released a statement taking exception to their approach to measuring surgical complications.

In the first study, researchers analyzed 30-day outcomes during a 10-year period at 263 hospitals participating in the ACS NSQIP and 526 nonparticipating propensity-matched hospitals across the United States. They focused on patients aged 65-99 years undergoing 11 high-risk general or vascular surgical procedures that are most in need of quality improvement: esophagectomy, pancreatic resection, colon resection, gastrectomy, liver resection, ventral hernia repair, cholecystectomy, appendectomy, abdominal aortic aneurysm repair, lower-extremity bypass, and carotid endarterectomy, said Dr. Nicholas H. Osborne of the Center for Healthcare Outcomes and Policy, University of Michigan, Ann Arbor, and a vascular surgeon at the university and his associates.

They found “slight trends toward improved outcomes” in NSQIP hospitals over time, but control hospitals showed the same trends. For example, 30-day mortality declined from 4.6% to 4.2% in participating hospitals during the study period, and similarly declined from 4.9% to 4.6% in nonparticipating hospitals. However, further analysis showed no statistically significant reductions after enrollment in the NSQIP in 30-day mortality, serious complications, reoperations, or readmissions, Dr. Osborne and his associates said (JAMA 2015 Feb. 3 [doi:10.1001/jama.2015.25]).

The underlying reasons for a lack of improvement among participating hospitals aren’t yet known, but it is possible that hospitals never implemented quality improvement efforts after being informed of their shortcomings, or that they implemented ineffective remedies. “Clinical quality improvement is challenging for hospitals. Changing physician practice requires complex, sustained, multifaceted interventions, and most hospitals may not have the expertise or resources to launch effective quality improvement interventions,” Dr. Osborne and his associates added.

In the second study, researchers analyzed surgical outcomes over a 4-year period among 113 academic hospitals in a health care system database; 39% of these hospitals participated in the NSQIP, receiving feedback on their performance, and the remaining 61% did not. This study evaluated 345,357 hospitalizations for 16 elective general and vascular surgeries, including many of the procedures covered in Dr. Osborne’s study plus mastectomy, thyroid procedures, open or laparoscopic colectomy, prostatectomy, and bariatric procedures, said Dr. David A. Etzioni, a surgeon at Mayo Clinic Arizona, Phoenix, and of the Kern Center for the Science of Health Care Delivery, and his associates.

This study also showed a slight decrease over time in postoperative complications, serious complications, and mortality at both NSQIP and non-NSQIP hospitals. “After accounting for patient risk, procedure type, underlying hospital performance, and temporal trends, the [statistical] model demonstrated no significant differences over time between NSQIP and non-NSQIP hospitals in terms of likelihood of complications, serious complications, or mortality,” Dr. Etzioni and his associates said (JAMA 2015 Feb. 3 [doi:10.1001/jama.2015.90]).

Their findings indicate that quality reports do not necessarily translate into evidence-based strategies for quality improvement and “suggest that a surgical outcomes reporting system does not provide a clear mechanism for quality improvement,” they noted.

In response to these reports, the American College of Surgeons released a statement emphasizing that claims data such as those used by both Osborne et al. and Etzioni et al. “are inaccurate and inappropriate for measuring surgical complications.” Furthermore, Dr. Clifford Ko, ACS director of the division of research and optimal patient care, called it “irresponsible to use data that are known to be an inaccurate measure of quality to determine the effectiveness of a quality improvement program.”

In addition, real-world experience shows that hospitals tend to focus on specific complications one at a time (such as surgical site infections) rather than amalgamating all complications. Hospitals also tend to address performance by separate specialties (such as urology) rather than on particular procedures (such as prostatectomy), according to the ACS statement.

Dr. Osborne’s study was supported in part by the National Institute on Aging. Dr. Osborne reported having no financial disclosures; one of his associates reported ties to Arbor Metrix. Dr. Etzioni’s study did not list any sources of financial support. Dr. Etzioni and his associates reported having no financial disclosures.

Among profoundly injured trauma patients with major bleeding, both early (24 hour) and late (30 day) mortality were similar between those who received transfusions of plasma, platelets, and red blood cells in a 1:1:1 ratio and those who received them in a 1:1:2 ratio in a phase III clinical trial, which was reported online Feb. 3 in JAMA.

Transfusion protocols for such patients have been “predominantly guided by tradition rather than evidence from large, multicenter randomized trials.” Moreover, transfusion protocols have changed markedly during the past decade, with many clinicians changing over to the 1:1:1 ratio because it is more balanced and more closely replicates the ratio present in whole blood than the traditional 1:1:2 ratio, said Dr. John B. Holcomb of the Center for Translational Injury Research, University of Texas Health Science Center, Houston, and his associates in the PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial.

©Vlad/Fotolia.com

They described the study as the first multicenter randomized trial using approved blood products to compare these two transfusion ratios, using mortality as the primary end point. They enrolled 680 adults treated at 12 Level 1 trauma centers in North America for severe injury with major bleeding during a 16-month period.

Overall 24-hour mortality was not significantly different, at 12.7% in the 1:1:1 group and 17% in the 1:1:2 group, and 30-day mortality also was not significantly different (22.4% vs 26.1%). These results were confirmed in sensitivity analyses. However, exsanguination, the predominant cause of death within 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6%), and significantly more patients in the 1:1:1 group achieved anatomic homeostasis (86.1% vs 78.1%). Thus, clinicians “should consider using a 1:1:1 transfusion protocol,” Dr. Holcomb and his associates said (JAMA 2015 Feb. 3 [doi:10.10001/jama.2015.12]).

There also were no significant differences between the two study groups in 23 complications, including transfusion-related complications. And,“despite significant concerns that the 1:1:1 group would experience higher rates of multiple inflammatory-mediated complications, such as acute respiratory distress syndrome, multiple organ failure, infection, venous thromboembolism, and sepsis, no differences were detected between the two treatment groups,” they noted.

Among profoundly injured trauma patients with major bleeding, both early (24 hour) and late (30 day) mortality were similar between those who received transfusions of plasma, platelets, and red blood cells in a 1:1:1 ratio and those who received them in a 1:1:2 ratio in a phase III clinical trial, which was reported online Feb. 3 in JAMA.

Transfusion protocols for such patients have been “predominantly guided by tradition rather than evidence from large, multicenter randomized trials.” Moreover, transfusion protocols have changed markedly during the past decade, with many clinicians changing over to the 1:1:1 ratio because it is more balanced and more closely replicates the ratio present in whole blood than the traditional 1:1:2 ratio, said Dr. John B. Holcomb of the Center for Translational Injury Research, University of Texas Health Science Center, Houston, and his associates in the PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial.

©Vlad/Fotolia.com

They described the study as the first multicenter randomized trial using approved blood products to compare these two transfusion ratios, using mortality as the primary end point. They enrolled 680 adults treated at 12 Level 1 trauma centers in North America for severe injury with major bleeding during a 16-month period.

Overall 24-hour mortality was not significantly different, at 12.7% in the 1:1:1 group and 17% in the 1:1:2 group, and 30-day mortality also was not significantly different (22.4% vs 26.1%). These results were confirmed in sensitivity analyses. However, exsanguination, the predominant cause of death within 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6%), and significantly more patients in the 1:1:1 group achieved anatomic homeostasis (86.1% vs 78.1%). Thus, clinicians “should consider using a 1:1:1 transfusion protocol,” Dr. Holcomb and his associates said (JAMA 2015 Feb. 3 [doi:10.10001/jama.2015.12]).

There also were no significant differences between the two study groups in 23 complications, including transfusion-related complications. And,“despite significant concerns that the 1:1:1 group would experience higher rates of multiple inflammatory-mediated complications, such as acute respiratory distress syndrome, multiple organ failure, infection, venous thromboembolism, and sepsis, no differences were detected between the two treatment groups,” they noted.

Among profoundly injured trauma patients with major bleeding, both early (24 hour) and late (30 day) mortality were similar between those who received transfusions of plasma, platelets, and red blood cells in a 1:1:1 ratio and those who received them in a 1:1:2 ratio in a phase III clinical trial, which was reported online Feb. 3 in JAMA.

Transfusion protocols for such patients have been “predominantly guided by tradition rather than evidence from large, multicenter randomized trials.” Moreover, transfusion protocols have changed markedly during the past decade, with many clinicians changing over to the 1:1:1 ratio because it is more balanced and more closely replicates the ratio present in whole blood than the traditional 1:1:2 ratio, said Dr. John B. Holcomb of the Center for Translational Injury Research, University of Texas Health Science Center, Houston, and his associates in the PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial.

©Vlad/Fotolia.com

They described the study as the first multicenter randomized trial using approved blood products to compare these two transfusion ratios, using mortality as the primary end point. They enrolled 680 adults treated at 12 Level 1 trauma centers in North America for severe injury with major bleeding during a 16-month period.

Overall 24-hour mortality was not significantly different, at 12.7% in the 1:1:1 group and 17% in the 1:1:2 group, and 30-day mortality also was not significantly different (22.4% vs 26.1%). These results were confirmed in sensitivity analyses. However, exsanguination, the predominant cause of death within 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6%), and significantly more patients in the 1:1:1 group achieved anatomic homeostasis (86.1% vs 78.1%). Thus, clinicians “should consider using a 1:1:1 transfusion protocol,” Dr. Holcomb and his associates said (JAMA 2015 Feb. 3 [doi:10.10001/jama.2015.12]).

There also were no significant differences between the two study groups in 23 complications, including transfusion-related complications. And,“despite significant concerns that the 1:1:1 group would experience higher rates of multiple inflammatory-mediated complications, such as acute respiratory distress syndrome, multiple organ failure, infection, venous thromboembolism, and sepsis, no differences were detected between the two treatment groups,” they noted.