Mary Ann Moon

Lowering LDL cholesterol level using statins appears to yield the same cardiovascular benefits in rheumatoid arthritis patients as in the general population, a study showed.

Cardiovascular (CV) disease is a common comorbidity in rheumatoid arthritis (RA) patients, who carry an estimated 50% increased risk of CV events or early mortality, compared with the general population. Yet epidemiologic studies have reported that RA patients generally have lower lipid levels than members of the general population, and studies assessing statin therapy in this patient population have yielded mixed results, said JaeJin An, PhD, of the department of pharmacy practice and administration, Western University of Health Sciences, Pomona, Calif., and her associates.

©Ugreen/thinkstockphotos.com

This may be because RA alters lipid metabolism in a complex manner, due to its associated systemic inflammation, the effects of RA drug therapy, and several genetic factors that characterize RA, they noted.

To assess the benefit of statin therapy for primary prevention in RA, the investigators performed a retrospective cohort study using the electronic medical records of adults enrolled in a single large California health care system. They focused on RA patients taking at least one disease-modifying antirheumatic drug who also had hyperlipidemia. In one cohort, 1,522 RA patients were matched for age and sex with 6,511 control subjects who were also in the health care system, and in a second cohort 1,746 RA patients were matched with 2,554 patients who had osteoarthritis (OA).

These study participants were followed for a median of 3-4 years for the development of MI, angina, stroke, transient ischemic attack, intermittent claudication, heart failure, or CV death. Lipid-lowering medications they were taking included atorvastatin, simvastatin, fluvastatin, lovastatin, rosuvastatin, and pravastatin. The study was supported by Bristol-Myers Squibb, maker of pravastatin.

Similar proportions of patients in the three study groups lowered their LDL-C level to clinically recommended levels based on their baseline CV risk: 79% of the RA group, 79% of the general control group, and 80% of the OA control group.

There were no differences in the link between lowering LDL-C level and improved CV outcomes among the three study groups. A reduction in LDL-C was associated with a 29% reduction in the risk of CV events in the RA group plus the general control group, and it was associated with a 50% reduction in the risk of CV events in the RA group plus the OA control group, the investigators reported (J Rheumatol. 2016 Sep 1. doi: 10.3899/jrheum.160110). In a further analysis of the data that adjusted for multiple CV risk factors, lowering LDL-C levels was associated with a similar degree of reduction in CV events in RA patients in the first cohort (hazard ratio, 0.68) and the second cohort (HR, 0.67).

“Our analyses further verified that having RA itself increased CV risk by 76% [compared with general control patients], even after adjusting for traditional risk factors such as age, sex, smoking, hypertension, and diabetes. These findings are consistent with previous findings, which suggest about a 50% higher risk of CV events and mortality among patients with RA relative to the general population,” Dr. An and her associates wrote.

Their results also are consistent with those of the recently reported TRACE-RA (Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Rheumatoid Arthritis) study, which found that lipid-lowering therapy with atorvastatin was associated with a 34% reduction in the primary composite CV endpoint in RA patients.

Bristol-Myers Squibb supported the study, and several coauthors are employees of the company.

[email protected]

Lowering LDL cholesterol level using statins appears to yield the same cardiovascular benefits in rheumatoid arthritis patients as in the general population, a study showed.

Cardiovascular (CV) disease is a common comorbidity in rheumatoid arthritis (RA) patients, who carry an estimated 50% increased risk of CV events or early mortality, compared with the general population. Yet epidemiologic studies have reported that RA patients generally have lower lipid levels than members of the general population, and studies assessing statin therapy in this patient population have yielded mixed results, said JaeJin An, PhD, of the department of pharmacy practice and administration, Western University of Health Sciences, Pomona, Calif., and her associates.

©Ugreen/thinkstockphotos.com

This may be because RA alters lipid metabolism in a complex manner, due to its associated systemic inflammation, the effects of RA drug therapy, and several genetic factors that characterize RA, they noted.

To assess the benefit of statin therapy for primary prevention in RA, the investigators performed a retrospective cohort study using the electronic medical records of adults enrolled in a single large California health care system. They focused on RA patients taking at least one disease-modifying antirheumatic drug who also had hyperlipidemia. In one cohort, 1,522 RA patients were matched for age and sex with 6,511 control subjects who were also in the health care system, and in a second cohort 1,746 RA patients were matched with 2,554 patients who had osteoarthritis (OA).

These study participants were followed for a median of 3-4 years for the development of MI, angina, stroke, transient ischemic attack, intermittent claudication, heart failure, or CV death. Lipid-lowering medications they were taking included atorvastatin, simvastatin, fluvastatin, lovastatin, rosuvastatin, and pravastatin. The study was supported by Bristol-Myers Squibb, maker of pravastatin.

Similar proportions of patients in the three study groups lowered their LDL-C level to clinically recommended levels based on their baseline CV risk: 79% of the RA group, 79% of the general control group, and 80% of the OA control group.

There were no differences in the link between lowering LDL-C level and improved CV outcomes among the three study groups. A reduction in LDL-C was associated with a 29% reduction in the risk of CV events in the RA group plus the general control group, and it was associated with a 50% reduction in the risk of CV events in the RA group plus the OA control group, the investigators reported (J Rheumatol. 2016 Sep 1. doi: 10.3899/jrheum.160110). In a further analysis of the data that adjusted for multiple CV risk factors, lowering LDL-C levels was associated with a similar degree of reduction in CV events in RA patients in the first cohort (hazard ratio, 0.68) and the second cohort (HR, 0.67).

“Our analyses further verified that having RA itself increased CV risk by 76% [compared with general control patients], even after adjusting for traditional risk factors such as age, sex, smoking, hypertension, and diabetes. These findings are consistent with previous findings, which suggest about a 50% higher risk of CV events and mortality among patients with RA relative to the general population,” Dr. An and her associates wrote.

Their results also are consistent with those of the recently reported TRACE-RA (Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Rheumatoid Arthritis) study, which found that lipid-lowering therapy with atorvastatin was associated with a 34% reduction in the primary composite CV endpoint in RA patients.

Bristol-Myers Squibb supported the study, and several coauthors are employees of the company.

[email protected]

Lowering LDL cholesterol level using statins appears to yield the same cardiovascular benefits in rheumatoid arthritis patients as in the general population, a study showed.

Cardiovascular (CV) disease is a common comorbidity in rheumatoid arthritis (RA) patients, who carry an estimated 50% increased risk of CV events or early mortality, compared with the general population. Yet epidemiologic studies have reported that RA patients generally have lower lipid levels than members of the general population, and studies assessing statin therapy in this patient population have yielded mixed results, said JaeJin An, PhD, of the department of pharmacy practice and administration, Western University of Health Sciences, Pomona, Calif., and her associates.

©Ugreen/thinkstockphotos.com

This may be because RA alters lipid metabolism in a complex manner, due to its associated systemic inflammation, the effects of RA drug therapy, and several genetic factors that characterize RA, they noted.

To assess the benefit of statin therapy for primary prevention in RA, the investigators performed a retrospective cohort study using the electronic medical records of adults enrolled in a single large California health care system. They focused on RA patients taking at least one disease-modifying antirheumatic drug who also had hyperlipidemia. In one cohort, 1,522 RA patients were matched for age and sex with 6,511 control subjects who were also in the health care system, and in a second cohort 1,746 RA patients were matched with 2,554 patients who had osteoarthritis (OA).

These study participants were followed for a median of 3-4 years for the development of MI, angina, stroke, transient ischemic attack, intermittent claudication, heart failure, or CV death. Lipid-lowering medications they were taking included atorvastatin, simvastatin, fluvastatin, lovastatin, rosuvastatin, and pravastatin. The study was supported by Bristol-Myers Squibb, maker of pravastatin.

Similar proportions of patients in the three study groups lowered their LDL-C level to clinically recommended levels based on their baseline CV risk: 79% of the RA group, 79% of the general control group, and 80% of the OA control group.

There were no differences in the link between lowering LDL-C level and improved CV outcomes among the three study groups. A reduction in LDL-C was associated with a 29% reduction in the risk of CV events in the RA group plus the general control group, and it was associated with a 50% reduction in the risk of CV events in the RA group plus the OA control group, the investigators reported (J Rheumatol. 2016 Sep 1. doi: 10.3899/jrheum.160110). In a further analysis of the data that adjusted for multiple CV risk factors, lowering LDL-C levels was associated with a similar degree of reduction in CV events in RA patients in the first cohort (hazard ratio, 0.68) and the second cohort (HR, 0.67).

“Our analyses further verified that having RA itself increased CV risk by 76% [compared with general control patients], even after adjusting for traditional risk factors such as age, sex, smoking, hypertension, and diabetes. These findings are consistent with previous findings, which suggest about a 50% higher risk of CV events and mortality among patients with RA relative to the general population,” Dr. An and her associates wrote.

Their results also are consistent with those of the recently reported TRACE-RA (Trial of Atorvastatin for the Primary Prevention of Cardiovascular Events in Rheumatoid Arthritis) study, which found that lipid-lowering therapy with atorvastatin was associated with a 34% reduction in the primary composite CV endpoint in RA patients.

Bristol-Myers Squibb supported the study, and several coauthors are employees of the company.

[email protected]

The rate of soccer injuries treated at U.S. emergency departments among patients aged 7-17 years rose by 111%, and that of soccer-related concussions and closed-head injuries increased by 1,595%, during the last 25 years, according to a report published online Sept. 12 in Pediatrics.

These increases underscore the need to improve injury prevention in this patient population. In particular, concussion prevention should focus on reducing player-to-player contact, especially during illegal moves. “Education of players, coaches, referees or officials, and parents about the importance of following the rules of the game, and enforcement of those rules, are critical first steps,” said Nicholas A. Smith of the Center for Injury Research and Policy, the Research Institute at Nationwide Children’s Hospital, Columbus, and his associates.

©James Boulette/iStockphoto.com

In what they described as the first study to comprehensively examine the epidemiology of U.S. youth soccer-related injuries treated at EDs, the investigators analyzed data from a nationally representative injury surveillance system between 1990 and 2014. Almost 3 million children were treated during that period for concussions/closed-head injuries, fractures, dislocations, sprains or strains, soft-tissue injuries such as abrasions or hematomas, lacerations, nondental avulsions, or punctures sustained during soccer practice or games.

The annual rate of soccer-related injury per 10,000 participants rose by 111%, and the annual number of such injuries rose by 78%. Much of this increase was attributed to a 1,595% rise in the annual rate of concussions/closed-head injuries and a 1,332% rise in the number of concussions/closed-head injuries. Patients with head injuries were twice as likely to be admitted to the hospital as were those with other types of injury, highlighting the severity of head injuries, the investigators noted.

The majority of injuries (73%) occurred in older children aged 12-17 years; their injury rate was more than three times higher than that in younger children, “probably because of the more aggressive play and the higher-energy impacts associated with the older age group,” Mr. Smith and his associates wrote (Pediatrics. 2016 Sep 12. doi: 10.1542/peds.2016-0346).

The increase in soccer-related injuries was much greater among girls than among boys, paralleling the much larger increase in soccer participation among girls than among boys during the study period.

This study underestimates the actual number of soccer-related injuries because it didn’t include patients who were treated in health care settings other than the ED and patients who were not treated at all, the investigators added.

The rate of soccer injuries treated at U.S. emergency departments among patients aged 7-17 years rose by 111%, and that of soccer-related concussions and closed-head injuries increased by 1,595%, during the last 25 years, according to a report published online Sept. 12 in Pediatrics.

These increases underscore the need to improve injury prevention in this patient population. In particular, concussion prevention should focus on reducing player-to-player contact, especially during illegal moves. “Education of players, coaches, referees or officials, and parents about the importance of following the rules of the game, and enforcement of those rules, are critical first steps,” said Nicholas A. Smith of the Center for Injury Research and Policy, the Research Institute at Nationwide Children’s Hospital, Columbus, and his associates.

©James Boulette/iStockphoto.com

In what they described as the first study to comprehensively examine the epidemiology of U.S. youth soccer-related injuries treated at EDs, the investigators analyzed data from a nationally representative injury surveillance system between 1990 and 2014. Almost 3 million children were treated during that period for concussions/closed-head injuries, fractures, dislocations, sprains or strains, soft-tissue injuries such as abrasions or hematomas, lacerations, nondental avulsions, or punctures sustained during soccer practice or games.

The annual rate of soccer-related injury per 10,000 participants rose by 111%, and the annual number of such injuries rose by 78%. Much of this increase was attributed to a 1,595% rise in the annual rate of concussions/closed-head injuries and a 1,332% rise in the number of concussions/closed-head injuries. Patients with head injuries were twice as likely to be admitted to the hospital as were those with other types of injury, highlighting the severity of head injuries, the investigators noted.

The majority of injuries (73%) occurred in older children aged 12-17 years; their injury rate was more than three times higher than that in younger children, “probably because of the more aggressive play and the higher-energy impacts associated with the older age group,” Mr. Smith and his associates wrote (Pediatrics. 2016 Sep 12. doi: 10.1542/peds.2016-0346).

The increase in soccer-related injuries was much greater among girls than among boys, paralleling the much larger increase in soccer participation among girls than among boys during the study period.

This study underestimates the actual number of soccer-related injuries because it didn’t include patients who were treated in health care settings other than the ED and patients who were not treated at all, the investigators added.

The rate of soccer injuries treated at U.S. emergency departments among patients aged 7-17 years rose by 111%, and that of soccer-related concussions and closed-head injuries increased by 1,595%, during the last 25 years, according to a report published online Sept. 12 in Pediatrics.

These increases underscore the need to improve injury prevention in this patient population. In particular, concussion prevention should focus on reducing player-to-player contact, especially during illegal moves. “Education of players, coaches, referees or officials, and parents about the importance of following the rules of the game, and enforcement of those rules, are critical first steps,” said Nicholas A. Smith of the Center for Injury Research and Policy, the Research Institute at Nationwide Children’s Hospital, Columbus, and his associates.

©James Boulette/iStockphoto.com

In what they described as the first study to comprehensively examine the epidemiology of U.S. youth soccer-related injuries treated at EDs, the investigators analyzed data from a nationally representative injury surveillance system between 1990 and 2014. Almost 3 million children were treated during that period for concussions/closed-head injuries, fractures, dislocations, sprains or strains, soft-tissue injuries such as abrasions or hematomas, lacerations, nondental avulsions, or punctures sustained during soccer practice or games.

The annual rate of soccer-related injury per 10,000 participants rose by 111%, and the annual number of such injuries rose by 78%. Much of this increase was attributed to a 1,595% rise in the annual rate of concussions/closed-head injuries and a 1,332% rise in the number of concussions/closed-head injuries. Patients with head injuries were twice as likely to be admitted to the hospital as were those with other types of injury, highlighting the severity of head injuries, the investigators noted.

The majority of injuries (73%) occurred in older children aged 12-17 years; their injury rate was more than three times higher than that in younger children, “probably because of the more aggressive play and the higher-energy impacts associated with the older age group,” Mr. Smith and his associates wrote (Pediatrics. 2016 Sep 12. doi: 10.1542/peds.2016-0346).

The increase in soccer-related injuries was much greater among girls than among boys, paralleling the much larger increase in soccer participation among girls than among boys during the study period.

This study underestimates the actual number of soccer-related injuries because it didn’t include patients who were treated in health care settings other than the ED and patients who were not treated at all, the investigators added.

The combination of an mTOR complex 1 inhibitor (everolimus) plus a VEGF inhibitor (bevacizumab) showed promise against advanced non–clear cell renal cell carcinoma characterized by papillary features in a small manufacturer-sponsored phase II trial, according to a report published online Sept. 6 in the Journal of Clinical Oncology.

Non–clear cell renal cell carcinomas (ncRCCs) are a diverse mixture of heterogeneous malignancies and include papillary, chromophobe, medullary, collecting duct, and a variety of unclassified tumor types. Researchers performed a single-center trial to assess the effectiveness of combined everolimus plus bevacizumab in 35 treatment-naive patients who presented with advanced disease representing all of these histologic types. The unclassified subgroup (23 patients) included several tumors with prominent papillary architectural features that did not fulfill other criteria for papillary RCC, said Martin H. Voss, MD, of Memorial Sloan Kettering Cancer Center, New York, and his associates.

A total of 18 patients (53%) were alive and free of disease progression at 6 months, and 10 (29%) were alive and progression free at 12 months. Two patients still were receiving study treatment at the time of publication, after 20.2 and 30.4 months of therapy, respectively.

“Objective responses were observed in a sizable proportion of subjects with significant papillary (7 of 18) or chromophobe (2 of 5) tumor components but rarely in patients with unclassified RCC without papillary features (1 of 9) or those with medullary RCC (0 of 2),” Dr. Voss and his associates reported. Among patients with unclassified RCC, the 14 whose cancer had a major papillary component showed an objective response rate of 43%, a median progression-free survival of 12.9 months, and a median overall survival of 28.2 months. In contrast, the nine patients whose cancer did not have a major papillary component showed an objective response rate of 11%, a median progression-free survival of 1.9 months, and a median overall survival of 9.3 months, the investigators said (J Clin Oncol. 2016 Sept 6. doi: 10.1200/JCO.2016.67.9084).

Treatment was generally well tolerated, even though there were frequent low-grade toxicities. High-grade toxicities known to be associated with mTOR complex 1 inhibitors or VEGF inhibitors included hyperglycemia (11%), hypertriglyceridemia (14%), lymphopenia (20%), hypertension (29%), and proteinuria (18%). There were two patient deaths from gastrointestinal hemorrhage, one of which was considered possibly related to bevacizumab.

Archived tissue samples were available for genetic analysis for some patients. Acquired mutations in the ARID1A gene were noted in 5 of 14 tumors with major papillary components, and all 5 of those patients achieved more than 6 months of progression-free survival with the combination therapy. In contrast, no ARID1A mutations were detected in any of the patients who had shorter progression-free survival, and none were detected in any of the tumors that did not have papillary components. This suggests that ARID1A “merits further study for its functional role in papillary RCC variants and as a candidate biomarker for future study of everolimus plus bevacizumab,” Dr. Voss and his associates said.

Novartis supported the study. Dr. Voss reported ties to Novartis, Calithera Biosciences, Natera, GlaxoSmithKline, Exelixis, Pfizer, Bristol-Myers Squibb, Genentech, and Takeda; his associates reported ties to numerous industry sources.

The combination of an mTOR complex 1 inhibitor (everolimus) plus a VEGF inhibitor (bevacizumab) showed promise against advanced non–clear cell renal cell carcinoma characterized by papillary features in a small manufacturer-sponsored phase II trial, according to a report published online Sept. 6 in the Journal of Clinical Oncology.

Non–clear cell renal cell carcinomas (ncRCCs) are a diverse mixture of heterogeneous malignancies and include papillary, chromophobe, medullary, collecting duct, and a variety of unclassified tumor types. Researchers performed a single-center trial to assess the effectiveness of combined everolimus plus bevacizumab in 35 treatment-naive patients who presented with advanced disease representing all of these histologic types. The unclassified subgroup (23 patients) included several tumors with prominent papillary architectural features that did not fulfill other criteria for papillary RCC, said Martin H. Voss, MD, of Memorial Sloan Kettering Cancer Center, New York, and his associates.

A total of 18 patients (53%) were alive and free of disease progression at 6 months, and 10 (29%) were alive and progression free at 12 months. Two patients still were receiving study treatment at the time of publication, after 20.2 and 30.4 months of therapy, respectively.

“Objective responses were observed in a sizable proportion of subjects with significant papillary (7 of 18) or chromophobe (2 of 5) tumor components but rarely in patients with unclassified RCC without papillary features (1 of 9) or those with medullary RCC (0 of 2),” Dr. Voss and his associates reported. Among patients with unclassified RCC, the 14 whose cancer had a major papillary component showed an objective response rate of 43%, a median progression-free survival of 12.9 months, and a median overall survival of 28.2 months. In contrast, the nine patients whose cancer did not have a major papillary component showed an objective response rate of 11%, a median progression-free survival of 1.9 months, and a median overall survival of 9.3 months, the investigators said (J Clin Oncol. 2016 Sept 6. doi: 10.1200/JCO.2016.67.9084).

Treatment was generally well tolerated, even though there were frequent low-grade toxicities. High-grade toxicities known to be associated with mTOR complex 1 inhibitors or VEGF inhibitors included hyperglycemia (11%), hypertriglyceridemia (14%), lymphopenia (20%), hypertension (29%), and proteinuria (18%). There were two patient deaths from gastrointestinal hemorrhage, one of which was considered possibly related to bevacizumab.

Archived tissue samples were available for genetic analysis for some patients. Acquired mutations in the ARID1A gene were noted in 5 of 14 tumors with major papillary components, and all 5 of those patients achieved more than 6 months of progression-free survival with the combination therapy. In contrast, no ARID1A mutations were detected in any of the patients who had shorter progression-free survival, and none were detected in any of the tumors that did not have papillary components. This suggests that ARID1A “merits further study for its functional role in papillary RCC variants and as a candidate biomarker for future study of everolimus plus bevacizumab,” Dr. Voss and his associates said.

Novartis supported the study. Dr. Voss reported ties to Novartis, Calithera Biosciences, Natera, GlaxoSmithKline, Exelixis, Pfizer, Bristol-Myers Squibb, Genentech, and Takeda; his associates reported ties to numerous industry sources.

The combination of an mTOR complex 1 inhibitor (everolimus) plus a VEGF inhibitor (bevacizumab) showed promise against advanced non–clear cell renal cell carcinoma characterized by papillary features in a small manufacturer-sponsored phase II trial, according to a report published online Sept. 6 in the Journal of Clinical Oncology.

Non–clear cell renal cell carcinomas (ncRCCs) are a diverse mixture of heterogeneous malignancies and include papillary, chromophobe, medullary, collecting duct, and a variety of unclassified tumor types. Researchers performed a single-center trial to assess the effectiveness of combined everolimus plus bevacizumab in 35 treatment-naive patients who presented with advanced disease representing all of these histologic types. The unclassified subgroup (23 patients) included several tumors with prominent papillary architectural features that did not fulfill other criteria for papillary RCC, said Martin H. Voss, MD, of Memorial Sloan Kettering Cancer Center, New York, and his associates.

A total of 18 patients (53%) were alive and free of disease progression at 6 months, and 10 (29%) were alive and progression free at 12 months. Two patients still were receiving study treatment at the time of publication, after 20.2 and 30.4 months of therapy, respectively.

“Objective responses were observed in a sizable proportion of subjects with significant papillary (7 of 18) or chromophobe (2 of 5) tumor components but rarely in patients with unclassified RCC without papillary features (1 of 9) or those with medullary RCC (0 of 2),” Dr. Voss and his associates reported. Among patients with unclassified RCC, the 14 whose cancer had a major papillary component showed an objective response rate of 43%, a median progression-free survival of 12.9 months, and a median overall survival of 28.2 months. In contrast, the nine patients whose cancer did not have a major papillary component showed an objective response rate of 11%, a median progression-free survival of 1.9 months, and a median overall survival of 9.3 months, the investigators said (J Clin Oncol. 2016 Sept 6. doi: 10.1200/JCO.2016.67.9084).

Treatment was generally well tolerated, even though there were frequent low-grade toxicities. High-grade toxicities known to be associated with mTOR complex 1 inhibitors or VEGF inhibitors included hyperglycemia (11%), hypertriglyceridemia (14%), lymphopenia (20%), hypertension (29%), and proteinuria (18%). There were two patient deaths from gastrointestinal hemorrhage, one of which was considered possibly related to bevacizumab.

Archived tissue samples were available for genetic analysis for some patients. Acquired mutations in the ARID1A gene were noted in 5 of 14 tumors with major papillary components, and all 5 of those patients achieved more than 6 months of progression-free survival with the combination therapy. In contrast, no ARID1A mutations were detected in any of the patients who had shorter progression-free survival, and none were detected in any of the tumors that did not have papillary components. This suggests that ARID1A “merits further study for its functional role in papillary RCC variants and as a candidate biomarker for future study of everolimus plus bevacizumab,” Dr. Voss and his associates said.

Novartis supported the study. Dr. Voss reported ties to Novartis, Calithera Biosciences, Natera, GlaxoSmithKline, Exelixis, Pfizer, Bristol-Myers Squibb, Genentech, and Takeda; his associates reported ties to numerous industry sources.

Higher levels of free thyroxine are associated with an increased risk of sudden cardiac death, even in euthyroid adults, according to a report published online Sept. 6 in Circulation.

Thyroid dysfunction, even in the subclinical range, is known to correlate with increased cardiovascular disease, but until now a possible link between free thyroxine levels and sudden cardiac death (SCD) has never been explored in the general population. Any factors that could improve prediction of SCD in the general population would be helpful because almost half of these cases are the first indication that the patient had heart disease, said Layal Chaker, MD, of the Rotterdam Thyroid Center and the departments of internal medicine and epidemiology, Erasmus University, Rotterdam, and her associates.

©jarun011/Thinkstock.com

They assessed SCD among 10,318 participants in the Rotterdam Study, a prospective population-based cohort study examining endocrine, cardiovascular, neurologic, ophthalmologic, and psychiatric diseases in middle-aged and older adults in the Netherlands. Men and women aged 45-106 years who had thyroid testing at baseline were followed for a median of 9.2 years (range, 4-21 years) for the development of SCD. There were 261 cases of SCD, and 231 of these occurred in euthyroid participants.

Higher levels of free thyroxine (T4) were associated with an increased risk of SCD, with a hazard ratio of 1.87 for every 1 ng/dL increase in free T4. When the analysis was confined to the 231 euthyroid participants, this association was even stronger, with an HR of 2.26, the investigators said (Circulation 2016 Sept 6. doi: 10.1161/CirculationAHA.115.020789).

The findings were similar in several sensitivity analyses, including one that excluded participants who had an unwitnessed SCD. In addition, adjustment of the data to account for the presence or absence of diabetes, as well as exclusion of patients who had heart failure, did not alter the risk estimates significantly. The results also were consistent across all age groups and both sexes, Dr. Chaker and her associates said.

The exact mechanism for the association between free thyroxine and SCD is not yet known but appears to be independent of traditional cardiovascular risk factors. “Bigger sample size and more detailed data are needed to determine whether these associations share the same or have distinct pathways,” they added.

The Netherlands Organisation for Health Research and Development and Erasmus Medical Center supported the study. Dr. Chaker and her associates reported having no relevant financial disclosures.

Higher levels of free thyroxine are associated with an increased risk of sudden cardiac death, even in euthyroid adults, according to a report published online Sept. 6 in Circulation.

Thyroid dysfunction, even in the subclinical range, is known to correlate with increased cardiovascular disease, but until now a possible link between free thyroxine levels and sudden cardiac death (SCD) has never been explored in the general population. Any factors that could improve prediction of SCD in the general population would be helpful because almost half of these cases are the first indication that the patient had heart disease, said Layal Chaker, MD, of the Rotterdam Thyroid Center and the departments of internal medicine and epidemiology, Erasmus University, Rotterdam, and her associates.

©jarun011/Thinkstock.com

They assessed SCD among 10,318 participants in the Rotterdam Study, a prospective population-based cohort study examining endocrine, cardiovascular, neurologic, ophthalmologic, and psychiatric diseases in middle-aged and older adults in the Netherlands. Men and women aged 45-106 years who had thyroid testing at baseline were followed for a median of 9.2 years (range, 4-21 years) for the development of SCD. There were 261 cases of SCD, and 231 of these occurred in euthyroid participants.

Higher levels of free thyroxine (T4) were associated with an increased risk of SCD, with a hazard ratio of 1.87 for every 1 ng/dL increase in free T4. When the analysis was confined to the 231 euthyroid participants, this association was even stronger, with an HR of 2.26, the investigators said (Circulation 2016 Sept 6. doi: 10.1161/CirculationAHA.115.020789).

The findings were similar in several sensitivity analyses, including one that excluded participants who had an unwitnessed SCD. In addition, adjustment of the data to account for the presence or absence of diabetes, as well as exclusion of patients who had heart failure, did not alter the risk estimates significantly. The results also were consistent across all age groups and both sexes, Dr. Chaker and her associates said.

The exact mechanism for the association between free thyroxine and SCD is not yet known but appears to be independent of traditional cardiovascular risk factors. “Bigger sample size and more detailed data are needed to determine whether these associations share the same or have distinct pathways,” they added.

The Netherlands Organisation for Health Research and Development and Erasmus Medical Center supported the study. Dr. Chaker and her associates reported having no relevant financial disclosures.

Higher levels of free thyroxine are associated with an increased risk of sudden cardiac death, even in euthyroid adults, according to a report published online Sept. 6 in Circulation.

Thyroid dysfunction, even in the subclinical range, is known to correlate with increased cardiovascular disease, but until now a possible link between free thyroxine levels and sudden cardiac death (SCD) has never been explored in the general population. Any factors that could improve prediction of SCD in the general population would be helpful because almost half of these cases are the first indication that the patient had heart disease, said Layal Chaker, MD, of the Rotterdam Thyroid Center and the departments of internal medicine and epidemiology, Erasmus University, Rotterdam, and her associates.

©jarun011/Thinkstock.com

They assessed SCD among 10,318 participants in the Rotterdam Study, a prospective population-based cohort study examining endocrine, cardiovascular, neurologic, ophthalmologic, and psychiatric diseases in middle-aged and older adults in the Netherlands. Men and women aged 45-106 years who had thyroid testing at baseline were followed for a median of 9.2 years (range, 4-21 years) for the development of SCD. There were 261 cases of SCD, and 231 of these occurred in euthyroid participants.

Higher levels of free thyroxine (T4) were associated with an increased risk of SCD, with a hazard ratio of 1.87 for every 1 ng/dL increase in free T4. When the analysis was confined to the 231 euthyroid participants, this association was even stronger, with an HR of 2.26, the investigators said (Circulation 2016 Sept 6. doi: 10.1161/CirculationAHA.115.020789).

The findings were similar in several sensitivity analyses, including one that excluded participants who had an unwitnessed SCD. In addition, adjustment of the data to account for the presence or absence of diabetes, as well as exclusion of patients who had heart failure, did not alter the risk estimates significantly. The results also were consistent across all age groups and both sexes, Dr. Chaker and her associates said.

The exact mechanism for the association between free thyroxine and SCD is not yet known but appears to be independent of traditional cardiovascular risk factors. “Bigger sample size and more detailed data are needed to determine whether these associations share the same or have distinct pathways,” they added.

The Netherlands Organisation for Health Research and Development and Erasmus Medical Center supported the study. Dr. Chaker and her associates reported having no relevant financial disclosures.

Whole brain radiotherapy, a standard treatment for patients with metastatic non–small-cell lung cancer, provided no clinical benefit in a noninferiority trial specifically designed to assess both patient survival and quality of life.

The findings were published online Sept. 4 in the Lancet.

Whole brain radiotherapy, with or without concomitant steroid treatment, has been widely used for decades in that patient population, even though no sufficiently powered, definitive studies support the approach. It is likely that patients and clinicians alike continue to embrace it because of the absence of alternative treatment options.

The Quality of Life After Treatment for Brain Metastases (QUARTZ) trial was intended to assess whether any improvement in survival offered by whole brain radiotherapy is balanced by deterioration in quality of life, said Paula Mulvenna, MBBS, of the Northern Center for Cancer Care, Newcastle (England) Hospitals, and her associates (Lancet 2016 Sep 4. doi: 10.1016/S0140-6736(16)30825-X).

QUARTZ involved 538 adults seen during a 7-year period who had NSCLC with brain metastases and who were not suited for either brain surgery or stereotactic radiotherapy. The median age was 66 years (range, 35-85 years), and 38% had a Karnofsky Performance Status score of less than 70.

The participants were randomly assigned to receive either optimal supportive care plus whole brain radiotherapy (269 patients) or optimal supportive care alone (269 patients) at 69 U.K. and 3 Australian medical centers. They reported on 20 symptoms and adverse effects, as well as health-related quality of life, approximately once per week.

The primary outcome measure – quality-adjusted life-years (QALY), which combines overall survival and quality of life – was 46.4 days with radiotherapy and 41.7 days without it.

Symptoms, adverse effects, and quality of life (QOL) were similar between the two study groups at 4 weeks, except that the radiotherapy group reported more moderate or severe episodes of drowsiness, hair loss, nausea, and dry or itchy scalp. The number and severity of serious adverse events were similar through 12 weeks of follow-up.

The percentage of patients whose QOL was either maintained or improved over time was similar between the two groups at 4 weeks (54% vs. 57%), 8 weeks (44% vs. 51%), and 12 weeks (44% vs. 49%). Changes in Karnofsky scores also were similar.

The study refuted the widely held belief that whole brain radiotherapy allows patients to reduce or discontinue steroid treatment, averting the associated adverse effects. Steroid doses were not significantly different between the two study groups through the first 8 weeks of treatment, which “challenges the dogma that whole brain radiotherapy can be seen as a steroid-sparing modality,” the investigators said.

Taken together, the findings “suggest that whole brain radiotherapy can be omitted and patients treated with optimal supportive care alone, without an important reduction in either overall survival or quality of life,” Dr. Mulvenna and her associates said.

The approximately 5-day difference between the two study groups in median overall survival highlights both the limited benefit offered by radiotherapy and the poor prognosis of this patient population, the researchers added.

Whole brain radiotherapy did offer a small survival benefit to the youngest patients who had good performance status and a “controlled” primary NSCLC. “For all other groups, [it] does not significantly affect QALY or overall survival,” they said.

Cancer Research U.K., the Medical Research Council in the U.K., the Trans Tasman Radiation Oncology Group, and the National Health and Medical Research Council Australia supported the study. Dr. Mulvenna and her associates reported having no relevant financial disclosures.

Whole brain radiotherapy, a standard treatment for patients with metastatic non–small-cell lung cancer, provided no clinical benefit in a noninferiority trial specifically designed to assess both patient survival and quality of life.

The findings were published online Sept. 4 in the Lancet.

Whole brain radiotherapy, with or without concomitant steroid treatment, has been widely used for decades in that patient population, even though no sufficiently powered, definitive studies support the approach. It is likely that patients and clinicians alike continue to embrace it because of the absence of alternative treatment options.

The Quality of Life After Treatment for Brain Metastases (QUARTZ) trial was intended to assess whether any improvement in survival offered by whole brain radiotherapy is balanced by deterioration in quality of life, said Paula Mulvenna, MBBS, of the Northern Center for Cancer Care, Newcastle (England) Hospitals, and her associates (Lancet 2016 Sep 4. doi: 10.1016/S0140-6736(16)30825-X).

QUARTZ involved 538 adults seen during a 7-year period who had NSCLC with brain metastases and who were not suited for either brain surgery or stereotactic radiotherapy. The median age was 66 years (range, 35-85 years), and 38% had a Karnofsky Performance Status score of less than 70.

The participants were randomly assigned to receive either optimal supportive care plus whole brain radiotherapy (269 patients) or optimal supportive care alone (269 patients) at 69 U.K. and 3 Australian medical centers. They reported on 20 symptoms and adverse effects, as well as health-related quality of life, approximately once per week.

The primary outcome measure – quality-adjusted life-years (QALY), which combines overall survival and quality of life – was 46.4 days with radiotherapy and 41.7 days without it.

Symptoms, adverse effects, and quality of life (QOL) were similar between the two study groups at 4 weeks, except that the radiotherapy group reported more moderate or severe episodes of drowsiness, hair loss, nausea, and dry or itchy scalp. The number and severity of serious adverse events were similar through 12 weeks of follow-up.

The percentage of patients whose QOL was either maintained or improved over time was similar between the two groups at 4 weeks (54% vs. 57%), 8 weeks (44% vs. 51%), and 12 weeks (44% vs. 49%). Changes in Karnofsky scores also were similar.

The study refuted the widely held belief that whole brain radiotherapy allows patients to reduce or discontinue steroid treatment, averting the associated adverse effects. Steroid doses were not significantly different between the two study groups through the first 8 weeks of treatment, which “challenges the dogma that whole brain radiotherapy can be seen as a steroid-sparing modality,” the investigators said.

Taken together, the findings “suggest that whole brain radiotherapy can be omitted and patients treated with optimal supportive care alone, without an important reduction in either overall survival or quality of life,” Dr. Mulvenna and her associates said.

The approximately 5-day difference between the two study groups in median overall survival highlights both the limited benefit offered by radiotherapy and the poor prognosis of this patient population, the researchers added.

Whole brain radiotherapy did offer a small survival benefit to the youngest patients who had good performance status and a “controlled” primary NSCLC. “For all other groups, [it] does not significantly affect QALY or overall survival,” they said.

Cancer Research U.K., the Medical Research Council in the U.K., the Trans Tasman Radiation Oncology Group, and the National Health and Medical Research Council Australia supported the study. Dr. Mulvenna and her associates reported having no relevant financial disclosures.

Whole brain radiotherapy, a standard treatment for patients with metastatic non–small-cell lung cancer, provided no clinical benefit in a noninferiority trial specifically designed to assess both patient survival and quality of life.

The findings were published online Sept. 4 in the Lancet.

Whole brain radiotherapy, with or without concomitant steroid treatment, has been widely used for decades in that patient population, even though no sufficiently powered, definitive studies support the approach. It is likely that patients and clinicians alike continue to embrace it because of the absence of alternative treatment options.

The Quality of Life After Treatment for Brain Metastases (QUARTZ) trial was intended to assess whether any improvement in survival offered by whole brain radiotherapy is balanced by deterioration in quality of life, said Paula Mulvenna, MBBS, of the Northern Center for Cancer Care, Newcastle (England) Hospitals, and her associates (Lancet 2016 Sep 4. doi: 10.1016/S0140-6736(16)30825-X).

QUARTZ involved 538 adults seen during a 7-year period who had NSCLC with brain metastases and who were not suited for either brain surgery or stereotactic radiotherapy. The median age was 66 years (range, 35-85 years), and 38% had a Karnofsky Performance Status score of less than 70.

The participants were randomly assigned to receive either optimal supportive care plus whole brain radiotherapy (269 patients) or optimal supportive care alone (269 patients) at 69 U.K. and 3 Australian medical centers. They reported on 20 symptoms and adverse effects, as well as health-related quality of life, approximately once per week.

The primary outcome measure – quality-adjusted life-years (QALY), which combines overall survival and quality of life – was 46.4 days with radiotherapy and 41.7 days without it.

Symptoms, adverse effects, and quality of life (QOL) were similar between the two study groups at 4 weeks, except that the radiotherapy group reported more moderate or severe episodes of drowsiness, hair loss, nausea, and dry or itchy scalp. The number and severity of serious adverse events were similar through 12 weeks of follow-up.

The percentage of patients whose QOL was either maintained or improved over time was similar between the two groups at 4 weeks (54% vs. 57%), 8 weeks (44% vs. 51%), and 12 weeks (44% vs. 49%). Changes in Karnofsky scores also were similar.

The study refuted the widely held belief that whole brain radiotherapy allows patients to reduce or discontinue steroid treatment, averting the associated adverse effects. Steroid doses were not significantly different between the two study groups through the first 8 weeks of treatment, which “challenges the dogma that whole brain radiotherapy can be seen as a steroid-sparing modality,” the investigators said.

Taken together, the findings “suggest that whole brain radiotherapy can be omitted and patients treated with optimal supportive care alone, without an important reduction in either overall survival or quality of life,” Dr. Mulvenna and her associates said.

The approximately 5-day difference between the two study groups in median overall survival highlights both the limited benefit offered by radiotherapy and the poor prognosis of this patient population, the researchers added.

Whole brain radiotherapy did offer a small survival benefit to the youngest patients who had good performance status and a “controlled” primary NSCLC. “For all other groups, [it] does not significantly affect QALY or overall survival,” they said.

Cancer Research U.K., the Medical Research Council in the U.K., the Trans Tasman Radiation Oncology Group, and the National Health and Medical Research Council Australia supported the study. Dr. Mulvenna and her associates reported having no relevant financial disclosures.

Antibiotic susceptibility in bacteria cultured from transplant recipients at a single hospital differed markedly from that in hospital-wide antibiograms, according to a report published in Diagnostic Microbiology and Infectious Disease.

Understanding the differences in antibiotic susceptibility among these highly immunocompromised patients can help guide treatment when they develop infection, and reduce the delay before they begin receiving appropriate antibiotics, said Rossana Rosa, MD, of Jackson Memorial Hospital, Miami, and her associates.

The investigators examined the antibiotic susceptibility of 1,889 isolates from blood and urine specimens taken from patients who had received solid-organ transplants at a single tertiary-care teaching hospital and then developed bacterial infections during a 2-year period. These patients included both children and adults who had received kidney, pancreas, liver, heart, lung, or intestinal transplants and were treated in numerous, “geographically distributed” units throughout the hospital. Their culture results were compared with those from 10,439 other patients with bacterial infections, which comprised the hospital-wide antibiograms developed every 6 months during the study period.

The Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa isolates from the transplant recipients showed markedly less susceptibility to first-line antibiotics than would have been predicted by the hospital-antibiograms. In particular, in the transplant recipients E. coli infections were resistant to trimethoprim-sulfamethoxazole, levofloxacin, and ceftriaxone; K. pneumoniae infections were resistant to every antibiotic except amikacin; and P. aeruginosa infections were resistant to levofloxacin, cefepime, and amikacin (Diag Microbiol Infect Dis. 2016 Aug 25. doi: 10.1016/j.diagmicrobio.2016.08.018).

“We advocate for the development of antibiograms specific to solid-organ transplant recipients. This may allow intrahospital comparisons and intertransplant-center monitoring of trends in antimicrobial resistance over time,” Dr. Rosa and her associates said.

Antibiotic susceptibility in bacteria cultured from transplant recipients at a single hospital differed markedly from that in hospital-wide antibiograms, according to a report published in Diagnostic Microbiology and Infectious Disease.

Understanding the differences in antibiotic susceptibility among these highly immunocompromised patients can help guide treatment when they develop infection, and reduce the delay before they begin receiving appropriate antibiotics, said Rossana Rosa, MD, of Jackson Memorial Hospital, Miami, and her associates.

The investigators examined the antibiotic susceptibility of 1,889 isolates from blood and urine specimens taken from patients who had received solid-organ transplants at a single tertiary-care teaching hospital and then developed bacterial infections during a 2-year period. These patients included both children and adults who had received kidney, pancreas, liver, heart, lung, or intestinal transplants and were treated in numerous, “geographically distributed” units throughout the hospital. Their culture results were compared with those from 10,439 other patients with bacterial infections, which comprised the hospital-wide antibiograms developed every 6 months during the study period.

The Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa isolates from the transplant recipients showed markedly less susceptibility to first-line antibiotics than would have been predicted by the hospital-antibiograms. In particular, in the transplant recipients E. coli infections were resistant to trimethoprim-sulfamethoxazole, levofloxacin, and ceftriaxone; K. pneumoniae infections were resistant to every antibiotic except amikacin; and P. aeruginosa infections were resistant to levofloxacin, cefepime, and amikacin (Diag Microbiol Infect Dis. 2016 Aug 25. doi: 10.1016/j.diagmicrobio.2016.08.018).

“We advocate for the development of antibiograms specific to solid-organ transplant recipients. This may allow intrahospital comparisons and intertransplant-center monitoring of trends in antimicrobial resistance over time,” Dr. Rosa and her associates said.

Antibiotic susceptibility in bacteria cultured from transplant recipients at a single hospital differed markedly from that in hospital-wide antibiograms, according to a report published in Diagnostic Microbiology and Infectious Disease.

Understanding the differences in antibiotic susceptibility among these highly immunocompromised patients can help guide treatment when they develop infection, and reduce the delay before they begin receiving appropriate antibiotics, said Rossana Rosa, MD, of Jackson Memorial Hospital, Miami, and her associates.

The investigators examined the antibiotic susceptibility of 1,889 isolates from blood and urine specimens taken from patients who had received solid-organ transplants at a single tertiary-care teaching hospital and then developed bacterial infections during a 2-year period. These patients included both children and adults who had received kidney, pancreas, liver, heart, lung, or intestinal transplants and were treated in numerous, “geographically distributed” units throughout the hospital. Their culture results were compared with those from 10,439 other patients with bacterial infections, which comprised the hospital-wide antibiograms developed every 6 months during the study period.

The Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa isolates from the transplant recipients showed markedly less susceptibility to first-line antibiotics than would have been predicted by the hospital-antibiograms. In particular, in the transplant recipients E. coli infections were resistant to trimethoprim-sulfamethoxazole, levofloxacin, and ceftriaxone; K. pneumoniae infections were resistant to every antibiotic except amikacin; and P. aeruginosa infections were resistant to levofloxacin, cefepime, and amikacin (Diag Microbiol Infect Dis. 2016 Aug 25. doi: 10.1016/j.diagmicrobio.2016.08.018).

“We advocate for the development of antibiograms specific to solid-organ transplant recipients. This may allow intrahospital comparisons and intertransplant-center monitoring of trends in antimicrobial resistance over time,” Dr. Rosa and her associates said.

Adding the long-acting beta-agonist salmeterol to fluticasone in a fixed-dose combination didn’t increase serious asthma-related events among children aged 4-11 years, according to a report published online Sept. 1 in the New England Journal of Medicine.

After long-acting beta-agonists were introduced as add-on therapy for uncontrolled asthma, two large studies involving adults linked the treatment to an increase in asthma-related death. Other studies found no such association.

The FDA mandated that all four manufacturers of those agents in the United States perform large postmarketing safety trials to establish the noninferiority of the approach. In response, GlaxoSmithKline, the only maker of a long-acting beta-agonist with a pediatric indication (salmeterol), performed this international randomized, double-blind, controlled trial at 567 medical centers in 32 countries, said David A. Stempel, MD, of Respiratory Clinical Development, GSK, Research Triangle Park, N.C., and his associates.

The trial involved 6,208 children aged 4-11 years who had controlled or uncontrolled asthma with a history of exacerbations during the preceding year. The participants were randomly assigned to receive 26 weeks of a lower fixed-dose combination of salmeterol plus fluticasone, a higher fixed-dose combination, a lower dose of fluticasone alone, or a higher dose of fluticasone alone, delivered twice daily via a disk device.

The primary safety endpoint was a composite of death, endotracheal intubation, and hospitalization. No deaths or intubations occurred.

A total of 27 patients taking combined therapy and 21 taking fluticasone alone required hospitalization for asthma (hazard ratio, 1.28). The number of severe asthma exacerbations was 14% lower when salmeterol was added to fluticasone, a nonsignificant difference.

The results demonstrate the noninferiority of the combined therapy, Dr. Stempel and his associates said (N Engl J Med. 2016 Sep 1;375[9]:840-9).

The percentage of children who withdrew from the study because of asthma exacerbations was identical in the two groups (1.1% of each), and the percentage who had a serious adverse event was nearly identical (1.8% vs 1.7%, respectively). The mean percentage of rescue therapy–free days also was similar (83.0% vs 81.9%), as was the mean percentage of days in which asthma was controlled (74.8% vs. 73.4%).

At the conclusion of the study, 88.1% of the fluticasone-plus-salmeterol group had controlled asthma, as did 88.5% of the fluticasone-only group. Meaningful differences between the two treatments could not be identified among various subgroups of patients – defined by age, sex, and race – because the overall number of adverse events was so low, the investigators added.

They cautioned that the trial excluded children who had a history of multiple asthma-related hospitalizations and intubations. Therefore, the findings may not be applicable to patients with very severe asthma, the researchers cautioned.

GlaxoSmithKline sponsored the trial in response to a Food and Drug Administration mandate for large postmarketing safety studies from the marketers of long-acting beta agonist–containing products sold in the United States. Dr. Stempel is an employee of GSK; his associates reported ties to numerous industry sources.

Adding the long-acting beta-agonist salmeterol to fluticasone in a fixed-dose combination didn’t increase serious asthma-related events among children aged 4-11 years, according to a report published online Sept. 1 in the New England Journal of Medicine.

After long-acting beta-agonists were introduced as add-on therapy for uncontrolled asthma, two large studies involving adults linked the treatment to an increase in asthma-related death. Other studies found no such association.

The FDA mandated that all four manufacturers of those agents in the United States perform large postmarketing safety trials to establish the noninferiority of the approach. In response, GlaxoSmithKline, the only maker of a long-acting beta-agonist with a pediatric indication (salmeterol), performed this international randomized, double-blind, controlled trial at 567 medical centers in 32 countries, said David A. Stempel, MD, of Respiratory Clinical Development, GSK, Research Triangle Park, N.C., and his associates.

The trial involved 6,208 children aged 4-11 years who had controlled or uncontrolled asthma with a history of exacerbations during the preceding year. The participants were randomly assigned to receive 26 weeks of a lower fixed-dose combination of salmeterol plus fluticasone, a higher fixed-dose combination, a lower dose of fluticasone alone, or a higher dose of fluticasone alone, delivered twice daily via a disk device.

The primary safety endpoint was a composite of death, endotracheal intubation, and hospitalization. No deaths or intubations occurred.

A total of 27 patients taking combined therapy and 21 taking fluticasone alone required hospitalization for asthma (hazard ratio, 1.28). The number of severe asthma exacerbations was 14% lower when salmeterol was added to fluticasone, a nonsignificant difference.

The results demonstrate the noninferiority of the combined therapy, Dr. Stempel and his associates said (N Engl J Med. 2016 Sep 1;375[9]:840-9).

The percentage of children who withdrew from the study because of asthma exacerbations was identical in the two groups (1.1% of each), and the percentage who had a serious adverse event was nearly identical (1.8% vs 1.7%, respectively). The mean percentage of rescue therapy–free days also was similar (83.0% vs 81.9%), as was the mean percentage of days in which asthma was controlled (74.8% vs. 73.4%).

At the conclusion of the study, 88.1% of the fluticasone-plus-salmeterol group had controlled asthma, as did 88.5% of the fluticasone-only group. Meaningful differences between the two treatments could not be identified among various subgroups of patients – defined by age, sex, and race – because the overall number of adverse events was so low, the investigators added.

They cautioned that the trial excluded children who had a history of multiple asthma-related hospitalizations and intubations. Therefore, the findings may not be applicable to patients with very severe asthma, the researchers cautioned.

GlaxoSmithKline sponsored the trial in response to a Food and Drug Administration mandate for large postmarketing safety studies from the marketers of long-acting beta agonist–containing products sold in the United States. Dr. Stempel is an employee of GSK; his associates reported ties to numerous industry sources.

Adding the long-acting beta-agonist salmeterol to fluticasone in a fixed-dose combination didn’t increase serious asthma-related events among children aged 4-11 years, according to a report published online Sept. 1 in the New England Journal of Medicine.

After long-acting beta-agonists were introduced as add-on therapy for uncontrolled asthma, two large studies involving adults linked the treatment to an increase in asthma-related death. Other studies found no such association.

The FDA mandated that all four manufacturers of those agents in the United States perform large postmarketing safety trials to establish the noninferiority of the approach. In response, GlaxoSmithKline, the only maker of a long-acting beta-agonist with a pediatric indication (salmeterol), performed this international randomized, double-blind, controlled trial at 567 medical centers in 32 countries, said David A. Stempel, MD, of Respiratory Clinical Development, GSK, Research Triangle Park, N.C., and his associates.

The trial involved 6,208 children aged 4-11 years who had controlled or uncontrolled asthma with a history of exacerbations during the preceding year. The participants were randomly assigned to receive 26 weeks of a lower fixed-dose combination of salmeterol plus fluticasone, a higher fixed-dose combination, a lower dose of fluticasone alone, or a higher dose of fluticasone alone, delivered twice daily via a disk device.

The primary safety endpoint was a composite of death, endotracheal intubation, and hospitalization. No deaths or intubations occurred.

A total of 27 patients taking combined therapy and 21 taking fluticasone alone required hospitalization for asthma (hazard ratio, 1.28). The number of severe asthma exacerbations was 14% lower when salmeterol was added to fluticasone, a nonsignificant difference.

The results demonstrate the noninferiority of the combined therapy, Dr. Stempel and his associates said (N Engl J Med. 2016 Sep 1;375[9]:840-9).

The percentage of children who withdrew from the study because of asthma exacerbations was identical in the two groups (1.1% of each), and the percentage who had a serious adverse event was nearly identical (1.8% vs 1.7%, respectively). The mean percentage of rescue therapy–free days also was similar (83.0% vs 81.9%), as was the mean percentage of days in which asthma was controlled (74.8% vs. 73.4%).

At the conclusion of the study, 88.1% of the fluticasone-plus-salmeterol group had controlled asthma, as did 88.5% of the fluticasone-only group. Meaningful differences between the two treatments could not be identified among various subgroups of patients – defined by age, sex, and race – because the overall number of adverse events was so low, the investigators added.

They cautioned that the trial excluded children who had a history of multiple asthma-related hospitalizations and intubations. Therefore, the findings may not be applicable to patients with very severe asthma, the researchers cautioned.

GlaxoSmithKline sponsored the trial in response to a Food and Drug Administration mandate for large postmarketing safety studies from the marketers of long-acting beta agonist–containing products sold in the United States. Dr. Stempel is an employee of GSK; his associates reported ties to numerous industry sources.

Adding formoterol to budesonide in a fixed-dose combination does not increase serous asthma-related events in adolescents and adults, according to a report published online Sept. 1 in the New England Journal of Medicine.

This finding from a multicenter randomized double-blind clinical trial involving 11,693 patients should allay safety concerns about adding long-acting beta-agonists to inhaled glucocorticoids in moderate to severe asthma. Previously, two large studies linked such additive therapy to increased asthma-related deaths and other serious outcomes, but other clinical trials and numerous meta-analyses found no such increase.

©MattZ90/thinkstockphotos.com

In 2009, the Food and Drug Administration mandated that the four manufacturers of long-acting beta-agonists available in the United States conduct postmarketing safety analyses of these agents. The current trial is AstraZeneca’s response to the mandate, said Stephen P. Peters, MD, PhD, of Wake Forest University, Winston-Salem N.C., and his associates.

They assessed patients aged 12 years and older who had taken daily asthma medication for at least 1 year before enrollment and had a history of at least one exacerbation during that year. These participants were enrolled at 534 medical centers in 25 countries during 2011-2015 and randomly assigned to receive either budesonide plus formoterol (5,846 patients) or budesonide alone (5,847 patients) through an inhaler twice daily for 26 weeks. The primary endpoint was a composite of asthma-related death, intubation, and hospitalization.

A total of 43 patients in the combined-therapy group had 49 serious asthma-related events, while 40 patients in the budesonide-only group had 45 such events. This is a nonsignificant difference and establishes the noninferiority of the combined treatment regarding this outcome, the investigators said (N Engl J Med. 2016 Sept 1. doi: 10.1056/NEJMoa1511190).

In addition, 539 (9.2%) of the patients in the combined-therapy group reported 637 asthma exacerbations, while 633 in the budesonide-only group had 762 exacerbations. Thus, the risk of having an asthma exacerbation was 16.5% lower with combined therapy (HR, 0.84).

Both study groups had a clinically relevant improvement in asthma control as measured by the ACQ-6, and the combined therapy yielded a significantly greater benefit. The percentage of patients who had a clinically relevant improvement in asthma control at the conclusion of treatment also favored budesonide plus formoterol (58.7% vs. 54.4%). And the combined-therapy group also had a greater mean number of symptom-free days, had fewer night-time awakenings, and used fewer doses of rescue medications, Dr. Peters and his associates said.

Given that asthma-related deaths are rare, none of the four individual manufacturer-sponsored postmarketing studies required by the FDA can be powered for a separate analysis of that endpoint. “Any between-group differences in asthma-related death will need to be evaluated in the context of pooled data from the four studies, once they are all completed,” the investigators added.

Dr. Peters and his associates reported ties to numerous industry sources.

Adding formoterol to budesonide in a fixed-dose combination does not increase serous asthma-related events in adolescents and adults, according to a report published online Sept. 1 in the New England Journal of Medicine.

This finding from a multicenter randomized double-blind clinical trial involving 11,693 patients should allay safety concerns about adding long-acting beta-agonists to inhaled glucocorticoids in moderate to severe asthma. Previously, two large studies linked such additive therapy to increased asthma-related deaths and other serious outcomes, but other clinical trials and numerous meta-analyses found no such increase.

©MattZ90/thinkstockphotos.com

In 2009, the Food and Drug Administration mandated that the four manufacturers of long-acting beta-agonists available in the United States conduct postmarketing safety analyses of these agents. The current trial is AstraZeneca’s response to the mandate, said Stephen P. Peters, MD, PhD, of Wake Forest University, Winston-Salem N.C., and his associates.

They assessed patients aged 12 years and older who had taken daily asthma medication for at least 1 year before enrollment and had a history of at least one exacerbation during that year. These participants were enrolled at 534 medical centers in 25 countries during 2011-2015 and randomly assigned to receive either budesonide plus formoterol (5,846 patients) or budesonide alone (5,847 patients) through an inhaler twice daily for 26 weeks. The primary endpoint was a composite of asthma-related death, intubation, and hospitalization.

A total of 43 patients in the combined-therapy group had 49 serious asthma-related events, while 40 patients in the budesonide-only group had 45 such events. This is a nonsignificant difference and establishes the noninferiority of the combined treatment regarding this outcome, the investigators said (N Engl J Med. 2016 Sept 1. doi: 10.1056/NEJMoa1511190).

In addition, 539 (9.2%) of the patients in the combined-therapy group reported 637 asthma exacerbations, while 633 in the budesonide-only group had 762 exacerbations. Thus, the risk of having an asthma exacerbation was 16.5% lower with combined therapy (HR, 0.84).

Both study groups had a clinically relevant improvement in asthma control as measured by the ACQ-6, and the combined therapy yielded a significantly greater benefit. The percentage of patients who had a clinically relevant improvement in asthma control at the conclusion of treatment also favored budesonide plus formoterol (58.7% vs. 54.4%). And the combined-therapy group also had a greater mean number of symptom-free days, had fewer night-time awakenings, and used fewer doses of rescue medications, Dr. Peters and his associates said.

Given that asthma-related deaths are rare, none of the four individual manufacturer-sponsored postmarketing studies required by the FDA can be powered for a separate analysis of that endpoint. “Any between-group differences in asthma-related death will need to be evaluated in the context of pooled data from the four studies, once they are all completed,” the investigators added.

Dr. Peters and his associates reported ties to numerous industry sources.

Adding formoterol to budesonide in a fixed-dose combination does not increase serous asthma-related events in adolescents and adults, according to a report published online Sept. 1 in the New England Journal of Medicine.

This finding from a multicenter randomized double-blind clinical trial involving 11,693 patients should allay safety concerns about adding long-acting beta-agonists to inhaled glucocorticoids in moderate to severe asthma. Previously, two large studies linked such additive therapy to increased asthma-related deaths and other serious outcomes, but other clinical trials and numerous meta-analyses found no such increase.

©MattZ90/thinkstockphotos.com

In 2009, the Food and Drug Administration mandated that the four manufacturers of long-acting beta-agonists available in the United States conduct postmarketing safety analyses of these agents. The current trial is AstraZeneca’s response to the mandate, said Stephen P. Peters, MD, PhD, of Wake Forest University, Winston-Salem N.C., and his associates.

They assessed patients aged 12 years and older who had taken daily asthma medication for at least 1 year before enrollment and had a history of at least one exacerbation during that year. These participants were enrolled at 534 medical centers in 25 countries during 2011-2015 and randomly assigned to receive either budesonide plus formoterol (5,846 patients) or budesonide alone (5,847 patients) through an inhaler twice daily for 26 weeks. The primary endpoint was a composite of asthma-related death, intubation, and hospitalization.

A total of 43 patients in the combined-therapy group had 49 serious asthma-related events, while 40 patients in the budesonide-only group had 45 such events. This is a nonsignificant difference and establishes the noninferiority of the combined treatment regarding this outcome, the investigators said (N Engl J Med. 2016 Sept 1. doi: 10.1056/NEJMoa1511190).

In addition, 539 (9.2%) of the patients in the combined-therapy group reported 637 asthma exacerbations, while 633 in the budesonide-only group had 762 exacerbations. Thus, the risk of having an asthma exacerbation was 16.5% lower with combined therapy (HR, 0.84).

Both study groups had a clinically relevant improvement in asthma control as measured by the ACQ-6, and the combined therapy yielded a significantly greater benefit. The percentage of patients who had a clinically relevant improvement in asthma control at the conclusion of treatment also favored budesonide plus formoterol (58.7% vs. 54.4%). And the combined-therapy group also had a greater mean number of symptom-free days, had fewer night-time awakenings, and used fewer doses of rescue medications, Dr. Peters and his associates said.

Given that asthma-related deaths are rare, none of the four individual manufacturer-sponsored postmarketing studies required by the FDA can be powered for a separate analysis of that endpoint. “Any between-group differences in asthma-related death will need to be evaluated in the context of pooled data from the four studies, once they are all completed,” the investigators added.

Dr. Peters and his associates reported ties to numerous industry sources.

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.

Off-hours presentation to the hospital with STEMI did not affect PCI outcomes in the international prospective randomized CHAMPION PHOENIX trial.

The newer findings are reassuring and, in contrast with findings from several previous retrospective registry–based studies, suggest that presenting to the hospital at night or on weekends or holidays is no more hazardous than presenting during regular working hours, Senthil Selvaraj, MD, said in a presentation at the annual congress of the European Society of Cardiology. The results may reflect global quality improvement measures in STEMI care.

In the study, which was simultaneously published in Journal of the American College of Cardiology, researchers assessed the outcomes of 1,992 patients with STEMI participating in a large, industry-sponsored clinical trial. The primary efficacy outcome – a combination of all-cause mortality, MI, stent thrombosis, or ischemia-driven revascularization at 48 hours – was no different between patients who presented at 7 a.m. through 7 p.m. Monday through Friday than in those who presented during off hours (RR, 1.00), said Dr. Selvaraj of Brigham and Women’s Hospital Heart & Vascular Center, Boston.

There also was no difference between the two study groups in the primary safety outcome, which was moderate to severe bleeding events.

PCI yielded consistent benefits regardless of the timing of patient presentation, Dr. Selvaraj said.

CHAMPION PHOENIX was sponsored by the Medicines Company.

Off-hours presentation to the hospital with STEMI did not affect PCI outcomes in the international prospective randomized CHAMPION PHOENIX trial.

The newer findings are reassuring and, in contrast with findings from several previous retrospective registry–based studies, suggest that presenting to the hospital at night or on weekends or holidays is no more hazardous than presenting during regular working hours, Senthil Selvaraj, MD, said in a presentation at the annual congress of the European Society of Cardiology. The results may reflect global quality improvement measures in STEMI care.

In the study, which was simultaneously published in Journal of the American College of Cardiology, researchers assessed the outcomes of 1,992 patients with STEMI participating in a large, industry-sponsored clinical trial. The primary efficacy outcome – a combination of all-cause mortality, MI, stent thrombosis, or ischemia-driven revascularization at 48 hours – was no different between patients who presented at 7 a.m. through 7 p.m. Monday through Friday than in those who presented during off hours (RR, 1.00), said Dr. Selvaraj of Brigham and Women’s Hospital Heart & Vascular Center, Boston.

There also was no difference between the two study groups in the primary safety outcome, which was moderate to severe bleeding events.

PCI yielded consistent benefits regardless of the timing of patient presentation, Dr. Selvaraj said.

CHAMPION PHOENIX was sponsored by the Medicines Company.

Off-hours presentation to the hospital with STEMI did not affect PCI outcomes in the international prospective randomized CHAMPION PHOENIX trial.

The newer findings are reassuring and, in contrast with findings from several previous retrospective registry–based studies, suggest that presenting to the hospital at night or on weekends or holidays is no more hazardous than presenting during regular working hours, Senthil Selvaraj, MD, said in a presentation at the annual congress of the European Society of Cardiology. The results may reflect global quality improvement measures in STEMI care.

In the study, which was simultaneously published in Journal of the American College of Cardiology, researchers assessed the outcomes of 1,992 patients with STEMI participating in a large, industry-sponsored clinical trial. The primary efficacy outcome – a combination of all-cause mortality, MI, stent thrombosis, or ischemia-driven revascularization at 48 hours – was no different between patients who presented at 7 a.m. through 7 p.m. Monday through Friday than in those who presented during off hours (RR, 1.00), said Dr. Selvaraj of Brigham and Women’s Hospital Heart & Vascular Center, Boston.

There also was no difference between the two study groups in the primary safety outcome, which was moderate to severe bleeding events.

PCI yielded consistent benefits regardless of the timing of patient presentation, Dr. Selvaraj said.

CHAMPION PHOENIX was sponsored by the Medicines Company.