Pulmonary Health Hub

The proton pump inhibitor lansoprazole was no better than placebo for improving symptoms and lung function in a randomized, placebo-controlled trial involving more than 300 children with poorly controlled asthma without overt gastroesophageal reflux.

Those treated with lansoprazole did, however, experience significantly more respiratory infections (relative risk, 1.3), sore throats (RR, 1.3), and episodes of bronchitis (RR, 2.2) than did those receiving placebo during the course of the 24-week study. The treatment group also experienced more activity-related bone fractures (6 vs. 1 in treatment vs. placebo groups, respectively), although this difference did not reach significance, Dr. Nicola Hanania and his* colleagues from the Writing Committee for the American Lung Association Asthma Clinical Research Centers reported in the Jan. 25 issue of JAMA.

The mean difference in change in Asthma Control Questionnaire scores between the 149 children treated with 15-30 mg/day of lansoprazole depending on weight and the 157 who received placebo in the Study of Acid Reflux in Children With Asthma was 0.2 units, which was less than the meaningful clinically important difference in both groups (–0.1 for lansoprazole, and –0.2 for placebo), and was not statistically significant. Mean differences in change for secondary outcomes, including forced expiratory volume in the first second, asthma-related quality of life, and rate of episodes of poor asthma control, also did not differ significantly between the groups, Dr. Hanania of Baylor College of Medicine, Houston, and his colleagues reported (JAMA 2012;307:373-81).

Additionally, lansoprazole had no treatment effect, compared with placebo, in a subanalysis of 49 study participants (20 in the placebo group and 29 in the lansoprazole group) who were found on esophageal pH studies to have gastroesophageal reflux (GER), they noted.

Untreated GER has been considered a possible cause of inadequate asthma control in children treated with inhaled corticosteroids, but proton pump inhibitors (PPIs) have not been well studied with respect to their use for asymptomatic GER in children with refractory asthma.

For the current double-masked study, children were enrolled between April 2007 and September 2010 at 19 academic clinical centers throughout the United States. They had a mean age of 11 years (range 6-17 years), 50% were black, 65% were boys, and all were using inhaled corticosteroids. Most had required an intervention for asthma symptoms in the year prior to enrollment, and the mean Asthma Control Questionnaire score was high, at 1.6 for both groups, which is consistent with poor asthma control.

The lansoprazole dose used for the study was based on weight, with patients weighing less than 30 kg receiving 15 mg/day, and those weighing 30 kg or more receiving 30 mg/day.

The findings indicate that the drug has no effect on asthma control measures, the investigators wrote. "This was the case even though GER was prevalent in the study sample," they noted. It was also the case in subgroups defined by markers of asthma severity.

"The results of this clinical trial are uniformly negative regarding the benefit of acid suppression therapy on symptom relief, lung function, airways reactivity, or quality of life," they said, concluding that in light of previous negative findings from a study of omeprazole, the use of PPI therapy in children with poorly controlled asthma is unwarranted.

The findings also raise important questions about the adverse effects of lansoprazole in children, and along with other concerning data that have led to two Food and Drug Administration Advisory Board Reviews in the past 2 years, they underscore the need for continued study of PPI safety in children, they said.

Although the activity-related fractures in the lansoprazole group were not significantly more common than in the placebo group (6 of 149 [4%] vs. 1 of 157 [less than 1%]; P = .06), they are a cause for concern. Of the seven fractures, one occurred on the day of randomization; the others occurred after 2 months (n = 1), 5 months (n = 3), and 6 months (n = 2) of follow-up. The affected children were 7-14 years old, and all had been taking inhaled corticosteroids during the trial; two had taken oral prednisone as well (one in each group).

This study was supported by the American Lung Association Asthma Clinical Research Centers, as well as by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute. Lansoprazole and placebo were provided by Takeda Pharmaceuticals; albuterol was provided by GlaxoSmithKline. Dr. Hanania and his coauthors had no disclosures to report.

*Correction, 1/27/2012: An earlier version of this story had an incorrect pronoun referencing Dr. Hanania.

The proton pump inhibitor lansoprazole was no better than placebo for improving symptoms and lung function in a randomized, placebo-controlled trial involving more than 300 children with poorly controlled asthma without overt gastroesophageal reflux.

Those treated with lansoprazole did, however, experience significantly more respiratory infections (relative risk, 1.3), sore throats (RR, 1.3), and episodes of bronchitis (RR, 2.2) than did those receiving placebo during the course of the 24-week study. The treatment group also experienced more activity-related bone fractures (6 vs. 1 in treatment vs. placebo groups, respectively), although this difference did not reach significance, Dr. Nicola Hanania and his* colleagues from the Writing Committee for the American Lung Association Asthma Clinical Research Centers reported in the Jan. 25 issue of JAMA.

The mean difference in change in Asthma Control Questionnaire scores between the 149 children treated with 15-30 mg/day of lansoprazole depending on weight and the 157 who received placebo in the Study of Acid Reflux in Children With Asthma was 0.2 units, which was less than the meaningful clinically important difference in both groups (–0.1 for lansoprazole, and –0.2 for placebo), and was not statistically significant. Mean differences in change for secondary outcomes, including forced expiratory volume in the first second, asthma-related quality of life, and rate of episodes of poor asthma control, also did not differ significantly between the groups, Dr. Hanania of Baylor College of Medicine, Houston, and his colleagues reported (JAMA 2012;307:373-81).

Additionally, lansoprazole had no treatment effect, compared with placebo, in a subanalysis of 49 study participants (20 in the placebo group and 29 in the lansoprazole group) who were found on esophageal pH studies to have gastroesophageal reflux (GER), they noted.

Untreated GER has been considered a possible cause of inadequate asthma control in children treated with inhaled corticosteroids, but proton pump inhibitors (PPIs) have not been well studied with respect to their use for asymptomatic GER in children with refractory asthma.

For the current double-masked study, children were enrolled between April 2007 and September 2010 at 19 academic clinical centers throughout the United States. They had a mean age of 11 years (range 6-17 years), 50% were black, 65% were boys, and all were using inhaled corticosteroids. Most had required an intervention for asthma symptoms in the year prior to enrollment, and the mean Asthma Control Questionnaire score was high, at 1.6 for both groups, which is consistent with poor asthma control.

The lansoprazole dose used for the study was based on weight, with patients weighing less than 30 kg receiving 15 mg/day, and those weighing 30 kg or more receiving 30 mg/day.

The findings indicate that the drug has no effect on asthma control measures, the investigators wrote. "This was the case even though GER was prevalent in the study sample," they noted. It was also the case in subgroups defined by markers of asthma severity.

"The results of this clinical trial are uniformly negative regarding the benefit of acid suppression therapy on symptom relief, lung function, airways reactivity, or quality of life," they said, concluding that in light of previous negative findings from a study of omeprazole, the use of PPI therapy in children with poorly controlled asthma is unwarranted.

The findings also raise important questions about the adverse effects of lansoprazole in children, and along with other concerning data that have led to two Food and Drug Administration Advisory Board Reviews in the past 2 years, they underscore the need for continued study of PPI safety in children, they said.

Although the activity-related fractures in the lansoprazole group were not significantly more common than in the placebo group (6 of 149 [4%] vs. 1 of 157 [less than 1%]; P = .06), they are a cause for concern. Of the seven fractures, one occurred on the day of randomization; the others occurred after 2 months (n = 1), 5 months (n = 3), and 6 months (n = 2) of follow-up. The affected children were 7-14 years old, and all had been taking inhaled corticosteroids during the trial; two had taken oral prednisone as well (one in each group).

This study was supported by the American Lung Association Asthma Clinical Research Centers, as well as by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute. Lansoprazole and placebo were provided by Takeda Pharmaceuticals; albuterol was provided by GlaxoSmithKline. Dr. Hanania and his coauthors had no disclosures to report.

*Correction, 1/27/2012: An earlier version of this story had an incorrect pronoun referencing Dr. Hanania.

The proton pump inhibitor lansoprazole was no better than placebo for improving symptoms and lung function in a randomized, placebo-controlled trial involving more than 300 children with poorly controlled asthma without overt gastroesophageal reflux.

Those treated with lansoprazole did, however, experience significantly more respiratory infections (relative risk, 1.3), sore throats (RR, 1.3), and episodes of bronchitis (RR, 2.2) than did those receiving placebo during the course of the 24-week study. The treatment group also experienced more activity-related bone fractures (6 vs. 1 in treatment vs. placebo groups, respectively), although this difference did not reach significance, Dr. Nicola Hanania and his* colleagues from the Writing Committee for the American Lung Association Asthma Clinical Research Centers reported in the Jan. 25 issue of JAMA.

The mean difference in change in Asthma Control Questionnaire scores between the 149 children treated with 15-30 mg/day of lansoprazole depending on weight and the 157 who received placebo in the Study of Acid Reflux in Children With Asthma was 0.2 units, which was less than the meaningful clinically important difference in both groups (–0.1 for lansoprazole, and –0.2 for placebo), and was not statistically significant. Mean differences in change for secondary outcomes, including forced expiratory volume in the first second, asthma-related quality of life, and rate of episodes of poor asthma control, also did not differ significantly between the groups, Dr. Hanania of Baylor College of Medicine, Houston, and his colleagues reported (JAMA 2012;307:373-81).

Additionally, lansoprazole had no treatment effect, compared with placebo, in a subanalysis of 49 study participants (20 in the placebo group and 29 in the lansoprazole group) who were found on esophageal pH studies to have gastroesophageal reflux (GER), they noted.

Untreated GER has been considered a possible cause of inadequate asthma control in children treated with inhaled corticosteroids, but proton pump inhibitors (PPIs) have not been well studied with respect to their use for asymptomatic GER in children with refractory asthma.

For the current double-masked study, children were enrolled between April 2007 and September 2010 at 19 academic clinical centers throughout the United States. They had a mean age of 11 years (range 6-17 years), 50% were black, 65% were boys, and all were using inhaled corticosteroids. Most had required an intervention for asthma symptoms in the year prior to enrollment, and the mean Asthma Control Questionnaire score was high, at 1.6 for both groups, which is consistent with poor asthma control.

The lansoprazole dose used for the study was based on weight, with patients weighing less than 30 kg receiving 15 mg/day, and those weighing 30 kg or more receiving 30 mg/day.

The findings indicate that the drug has no effect on asthma control measures, the investigators wrote. "This was the case even though GER was prevalent in the study sample," they noted. It was also the case in subgroups defined by markers of asthma severity.

"The results of this clinical trial are uniformly negative regarding the benefit of acid suppression therapy on symptom relief, lung function, airways reactivity, or quality of life," they said, concluding that in light of previous negative findings from a study of omeprazole, the use of PPI therapy in children with poorly controlled asthma is unwarranted.

The findings also raise important questions about the adverse effects of lansoprazole in children, and along with other concerning data that have led to two Food and Drug Administration Advisory Board Reviews in the past 2 years, they underscore the need for continued study of PPI safety in children, they said.

Although the activity-related fractures in the lansoprazole group were not significantly more common than in the placebo group (6 of 149 [4%] vs. 1 of 157 [less than 1%]; P = .06), they are a cause for concern. Of the seven fractures, one occurred on the day of randomization; the others occurred after 2 months (n = 1), 5 months (n = 3), and 6 months (n = 2) of follow-up. The affected children were 7-14 years old, and all had been taking inhaled corticosteroids during the trial; two had taken oral prednisone as well (one in each group).

This study was supported by the American Lung Association Asthma Clinical Research Centers, as well as by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute. Lansoprazole and placebo were provided by Takeda Pharmaceuticals; albuterol was provided by GlaxoSmithKline. Dr. Hanania and his coauthors had no disclosures to report.

*Correction, 1/27/2012: An earlier version of this story had an incorrect pronoun referencing Dr. Hanania.

Unlike cigarette smoking, 20 years of typical marijuana smoking doesn’t appear to impair lung function, according to a report in the Jan. 11 issue of JAMA.

"With up to 7 joint-years of lifetime exposure (e.g., one joint per day for 7 years or one joint per week for 49 years), we found no evidence that increasing exposure to marijuana adversely affects pulmonary function," said Dr. Mark J. Pletcher of the department of epidemiology and biostatistics and the department of medicine, University of California, San Francisco, and his associates.

While heavier use may impair lung function, the number of such users was too small in this study cohort to allow reliable estimates. The data suggested a detrimental effect with heavier marijuana smoking, the investigators noted.

© Scott Harms/iStockphoto.com

Previous studies of the pulmonary effects of long-term marijuana use have yielded inconsistent results. On the one hand, they have demonstrated "consistent evidence of airway mucosal injury and inflammation, as well as increased respiratory symptoms such as cough, phlegm production, and wheeze, similar to that seen in tobacco smokers." On the other hand, these appear to be short-term effects, and there has been no clear evidence of long-term damage to lung function.

Dr. Pletcher and his colleagues studied the issue using data from a large longitudinal study of coronary risk that closely followed the cigarette and marijuana smoking habits of 5,016 young adults in four U.S. communities from 1985 through 2006. As part of that study, the subjects (aged 18-30 years at baseline) underwent pulmonary function testing at baseline, 2 years, 5 years, 10 years, and 20 years.

Using that data, "we estimated both current intensity and lifetime cumulative exposure to tobacco and marijuana smoking and analyzed their associations with spirometric measures of pulmonary function over the 20 years of follow-up," the researchers said.

One joint-year of exposure was defined as the equivalent of 365 joints or filled pipe bowls smoked. Secondhand smoke exposure also was taken into account.

As expected, both current and lifetime tobacco smoking were associated with lower forced expiratory volume in 1 second (FEV₁) and lower forced vital capacity (FVC). But unexpectedly, both current and lifetime marijuana smoking were associated with higher FEV₁ and higher FVC, the authors wrote (JAMA 2012;307:173-81).

"For example, compared with zero exposure, FVC increased with greater lifetime exposure in joint-years, and FEV₁ increased with greater lifetime exposure of up to 10 joint-years and then declined to ... greater than zero-exposure level," the investigators said.

Why marijuana smoking would increase lung capacity is unknown, but other studies have also found this effect. "Some investigators have proposed that the deep inspiratory maneuvers practiced by marijuana smokers could stretch the lungs, resulting in larger lung volumes. Another speculative possibility is strengthening of chest wall musculature or another ‘training’ effect that allows marijuana users to inspire more fully (closer to lung capacity) on spirometry testing," Dr. Pletcher and his associates said.

In a separate analysis of the data using different statistical methods, "we again found strong, dose-related associations between increasing exposure to tobacco and lower FEV₁ and FVC," but no such associations for marijuana smoking. Only at very high levels of marijuana smoking was a detrimental effect on pulmonary function suggested.

"Hypothetically speaking, a positive effect from marijuana in the short term (the stretch/training effect) and a negative effect in the long term (damage from smoke exposure) should result in a nonlinear association such as the one we observed. According to this explanation, the predominant effect for FEV₁ at very high exposure (more than 40 joint-years) reflects cumulative damage; the predominant effect for FVC at all levels of exposure is from the stretch/training mechanism," they noted.

"Marijuana may have beneficial effects on pain control, appetite, mood, and management of other chronic symptoms. Our findings suggest that occasional use of marijuana for these or other purposes may not be associated with adverse consequences on pulmonary function," the investigators said.

This study was supported by the National Institute on Drug Abuse and the National Heart, Lung, and Blood Institute. Dr. Pletcher reported no conflicts of interest.

Unlike cigarette smoking, 20 years of typical marijuana smoking doesn’t appear to impair lung function, according to a report in the Jan. 11 issue of JAMA.

"With up to 7 joint-years of lifetime exposure (e.g., one joint per day for 7 years or one joint per week for 49 years), we found no evidence that increasing exposure to marijuana adversely affects pulmonary function," said Dr. Mark J. Pletcher of the department of epidemiology and biostatistics and the department of medicine, University of California, San Francisco, and his associates.

While heavier use may impair lung function, the number of such users was too small in this study cohort to allow reliable estimates. The data suggested a detrimental effect with heavier marijuana smoking, the investigators noted.

© Scott Harms/iStockphoto.com

Previous studies of the pulmonary effects of long-term marijuana use have yielded inconsistent results. On the one hand, they have demonstrated "consistent evidence of airway mucosal injury and inflammation, as well as increased respiratory symptoms such as cough, phlegm production, and wheeze, similar to that seen in tobacco smokers." On the other hand, these appear to be short-term effects, and there has been no clear evidence of long-term damage to lung function.

Dr. Pletcher and his colleagues studied the issue using data from a large longitudinal study of coronary risk that closely followed the cigarette and marijuana smoking habits of 5,016 young adults in four U.S. communities from 1985 through 2006. As part of that study, the subjects (aged 18-30 years at baseline) underwent pulmonary function testing at baseline, 2 years, 5 years, 10 years, and 20 years.

Using that data, "we estimated both current intensity and lifetime cumulative exposure to tobacco and marijuana smoking and analyzed their associations with spirometric measures of pulmonary function over the 20 years of follow-up," the researchers said.

One joint-year of exposure was defined as the equivalent of 365 joints or filled pipe bowls smoked. Secondhand smoke exposure also was taken into account.

As expected, both current and lifetime tobacco smoking were associated with lower forced expiratory volume in 1 second (FEV₁) and lower forced vital capacity (FVC). But unexpectedly, both current and lifetime marijuana smoking were associated with higher FEV₁ and higher FVC, the authors wrote (JAMA 2012;307:173-81).

"For example, compared with zero exposure, FVC increased with greater lifetime exposure in joint-years, and FEV₁ increased with greater lifetime exposure of up to 10 joint-years and then declined to ... greater than zero-exposure level," the investigators said.

Why marijuana smoking would increase lung capacity is unknown, but other studies have also found this effect. "Some investigators have proposed that the deep inspiratory maneuvers practiced by marijuana smokers could stretch the lungs, resulting in larger lung volumes. Another speculative possibility is strengthening of chest wall musculature or another ‘training’ effect that allows marijuana users to inspire more fully (closer to lung capacity) on spirometry testing," Dr. Pletcher and his associates said.

In a separate analysis of the data using different statistical methods, "we again found strong, dose-related associations between increasing exposure to tobacco and lower FEV₁ and FVC," but no such associations for marijuana smoking. Only at very high levels of marijuana smoking was a detrimental effect on pulmonary function suggested.

"Hypothetically speaking, a positive effect from marijuana in the short term (the stretch/training effect) and a negative effect in the long term (damage from smoke exposure) should result in a nonlinear association such as the one we observed. According to this explanation, the predominant effect for FEV₁ at very high exposure (more than 40 joint-years) reflects cumulative damage; the predominant effect for FVC at all levels of exposure is from the stretch/training mechanism," they noted.

"Marijuana may have beneficial effects on pain control, appetite, mood, and management of other chronic symptoms. Our findings suggest that occasional use of marijuana for these or other purposes may not be associated with adverse consequences on pulmonary function," the investigators said.

This study was supported by the National Institute on Drug Abuse and the National Heart, Lung, and Blood Institute. Dr. Pletcher reported no conflicts of interest.

Unlike cigarette smoking, 20 years of typical marijuana smoking doesn’t appear to impair lung function, according to a report in the Jan. 11 issue of JAMA.

"With up to 7 joint-years of lifetime exposure (e.g., one joint per day for 7 years or one joint per week for 49 years), we found no evidence that increasing exposure to marijuana adversely affects pulmonary function," said Dr. Mark J. Pletcher of the department of epidemiology and biostatistics and the department of medicine, University of California, San Francisco, and his associates.

While heavier use may impair lung function, the number of such users was too small in this study cohort to allow reliable estimates. The data suggested a detrimental effect with heavier marijuana smoking, the investigators noted.

© Scott Harms/iStockphoto.com

Previous studies of the pulmonary effects of long-term marijuana use have yielded inconsistent results. On the one hand, they have demonstrated "consistent evidence of airway mucosal injury and inflammation, as well as increased respiratory symptoms such as cough, phlegm production, and wheeze, similar to that seen in tobacco smokers." On the other hand, these appear to be short-term effects, and there has been no clear evidence of long-term damage to lung function.

Dr. Pletcher and his colleagues studied the issue using data from a large longitudinal study of coronary risk that closely followed the cigarette and marijuana smoking habits of 5,016 young adults in four U.S. communities from 1985 through 2006. As part of that study, the subjects (aged 18-30 years at baseline) underwent pulmonary function testing at baseline, 2 years, 5 years, 10 years, and 20 years.

Using that data, "we estimated both current intensity and lifetime cumulative exposure to tobacco and marijuana smoking and analyzed their associations with spirometric measures of pulmonary function over the 20 years of follow-up," the researchers said.

One joint-year of exposure was defined as the equivalent of 365 joints or filled pipe bowls smoked. Secondhand smoke exposure also was taken into account.

As expected, both current and lifetime tobacco smoking were associated with lower forced expiratory volume in 1 second (FEV₁) and lower forced vital capacity (FVC). But unexpectedly, both current and lifetime marijuana smoking were associated with higher FEV₁ and higher FVC, the authors wrote (JAMA 2012;307:173-81).

"For example, compared with zero exposure, FVC increased with greater lifetime exposure in joint-years, and FEV₁ increased with greater lifetime exposure of up to 10 joint-years and then declined to ... greater than zero-exposure level," the investigators said.

Why marijuana smoking would increase lung capacity is unknown, but other studies have also found this effect. "Some investigators have proposed that the deep inspiratory maneuvers practiced by marijuana smokers could stretch the lungs, resulting in larger lung volumes. Another speculative possibility is strengthening of chest wall musculature or another ‘training’ effect that allows marijuana users to inspire more fully (closer to lung capacity) on spirometry testing," Dr. Pletcher and his associates said.

In a separate analysis of the data using different statistical methods, "we again found strong, dose-related associations between increasing exposure to tobacco and lower FEV₁ and FVC," but no such associations for marijuana smoking. Only at very high levels of marijuana smoking was a detrimental effect on pulmonary function suggested.

"Hypothetically speaking, a positive effect from marijuana in the short term (the stretch/training effect) and a negative effect in the long term (damage from smoke exposure) should result in a nonlinear association such as the one we observed. According to this explanation, the predominant effect for FEV₁ at very high exposure (more than 40 joint-years) reflects cumulative damage; the predominant effect for FVC at all levels of exposure is from the stretch/training mechanism," they noted.

"Marijuana may have beneficial effects on pain control, appetite, mood, and management of other chronic symptoms. Our findings suggest that occasional use of marijuana for these or other purposes may not be associated with adverse consequences on pulmonary function," the investigators said.

This study was supported by the National Institute on Drug Abuse and the National Heart, Lung, and Blood Institute. Dr. Pletcher reported no conflicts of interest.

SAN DIEGO – Prophylaxis with rivaroxaban achieved significant reductions in venous thromboembolism, compared with two commonly used drugs when put to the test in 5,346 consecutive, unselected patients undergoing major orthopedic surgery.

The incidence of in-hospital symptomatic venous thromboembolism (VTE) was 2.4% with rivaroxaban (Xarelto), compared with 3.9% with low molecular weight heparin (LMWH), and 5.5% with fondaparinux (Arixtra). This corresponds to a relative risk reduction of 39%, compared with LMWH, and 57% compared with fondaparinux.

Rivaroxaban, an oral Factor Xa inhibitor, also has superior safety with regard to major bleeding and surgical complications, according to Dr. Jan Beyer-Westendorf, with the University Clinic at Dresden (Germany) Technical University.

"Patients in real-world major orthopedic surgery benefit from VTE-prophylaxis with rivaroxaban even more than could be expected from the phase III results of the RECORD trial," he said at the annual meeting of the American Society of Hematology.

The four phase III RECORD (REgulation of Coagulation in ORthopedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism) trials compared rivaroxaban with enoxaparin in more than 12,500 patients undergoing knee and hip replacement. The trials did not evaluate fondaparinux or LMWH, despite being the standard of care at many hospitals.

Rivaroxaban was approved in the United States in July 2011 for DVT prophylaxis in adults undergoing hip and knee replacement surgery, and gained a second indication in November 2011 for stroke prophylaxis in patients with nonvalvular atrial fibrillation.

Dr. Beyer-Westendorf and his colleagues analyzed 5,346 consecutive patients who underwent major orthopedic surgery at the university clinic during three periods: 2005-2007 when LMWH was the standard prophylaxis; 2008-2009 when fondaparinux was the standard; and finally from 2010 to June 2011 when rivaroxaban became the clinic’s standard prophylaxis.

In all, 1,055 patients were treated with rivaroxaban, 1,683 with LMWH, and 2,069 with fondaparinux. Of note, previous VTE was more common at baseline in the rivaroxaban group at 4% vs. 1.4% in the LMWH group, and 1.1% in the fondaparinux group, he said.

Rivaroxaban reduced the relative risk of the composite of proximal DVT, pulmonary embolism, and VTE-related death by 29%, compared with LMWH, and 42% compared with fondaparinux, but the difference between the three groups did not achieve statistical significance (1.0% vs. 1.4% vs. 1.7%), Dr. Beyer-Westendorf said.

In a pooled analysis of RECORD 1, 2, and 3, rivaroxaban significantly reduced the composite of symptomatic VTE and all-cause mortality during the 2-week period after surgery, compared with enoxaparin (0.4% vs. 0.8%), according to the Bayer HealthCare website.

In the current analysis, severe bleeding was significantly lower with rivaroxaban at 7.4% vs. 14.9% with LMWH, and 11.1% with fondaparinux.

Bleeding leading to surgical revisions was also significantly lower at 0.4% vs. 1.7% with LMWH, and 1.1% with fondaparinux.

Dr. Beyer-Westendorf pointed out that severe bleeding rates were less than 1% in the RECORD 1-4 trials using a more narrow definition of severe bleeding as overt bleeding outside of the surgical site. Their analysis used the International Society on Thrombosis and Hemostasis criteria for severe bleeding.

Finally, the reduction in VTE events, bleeding, and surgical revisions was correlated with a significantly shorter median hospital stay in patients given rivaroxaban prophylaxis vs. LMWH or fondaparinux (8.3 days vs. 11.6 days vs. 9.3 days).

Dr. Beyer-Westendorf said it was unlikely that changes in anesthesia or surgical practice over the study period could have attenuated the results. In addition, the researchers conducted a matched-pair analysis to evaluate whether the benefits of rivaroxaban were due to selection or detection bias. Outcomes remained superior for rivaroxaban after matching patients according to age, gender, type of surgery, and history of VTE. Complete compression ultrasound testing also remained constant at about 13% from 2005 to 2010 before falling to 8.2% in 2011 due to fewer complete compression ultrasound–positive findings, Dr. Beyer-Westendorf noted.

"These findings in a large real-world surgery cohort are robust and not significantly influenced by a selection or detection bias," he said.

Dr. Beyer-Westendorf disclosed research grants from and serving as a speaker for Bayer HealthCare, which markets Xarelto.

SAN DIEGO – Prophylaxis with rivaroxaban achieved significant reductions in venous thromboembolism, compared with two commonly used drugs when put to the test in 5,346 consecutive, unselected patients undergoing major orthopedic surgery.

The incidence of in-hospital symptomatic venous thromboembolism (VTE) was 2.4% with rivaroxaban (Xarelto), compared with 3.9% with low molecular weight heparin (LMWH), and 5.5% with fondaparinux (Arixtra). This corresponds to a relative risk reduction of 39%, compared with LMWH, and 57% compared with fondaparinux.

Rivaroxaban, an oral Factor Xa inhibitor, also has superior safety with regard to major bleeding and surgical complications, according to Dr. Jan Beyer-Westendorf, with the University Clinic at Dresden (Germany) Technical University.

"Patients in real-world major orthopedic surgery benefit from VTE-prophylaxis with rivaroxaban even more than could be expected from the phase III results of the RECORD trial," he said at the annual meeting of the American Society of Hematology.

The four phase III RECORD (REgulation of Coagulation in ORthopedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism) trials compared rivaroxaban with enoxaparin in more than 12,500 patients undergoing knee and hip replacement. The trials did not evaluate fondaparinux or LMWH, despite being the standard of care at many hospitals.

Rivaroxaban was approved in the United States in July 2011 for DVT prophylaxis in adults undergoing hip and knee replacement surgery, and gained a second indication in November 2011 for stroke prophylaxis in patients with nonvalvular atrial fibrillation.

Dr. Beyer-Westendorf and his colleagues analyzed 5,346 consecutive patients who underwent major orthopedic surgery at the university clinic during three periods: 2005-2007 when LMWH was the standard prophylaxis; 2008-2009 when fondaparinux was the standard; and finally from 2010 to June 2011 when rivaroxaban became the clinic’s standard prophylaxis.

In all, 1,055 patients were treated with rivaroxaban, 1,683 with LMWH, and 2,069 with fondaparinux. Of note, previous VTE was more common at baseline in the rivaroxaban group at 4% vs. 1.4% in the LMWH group, and 1.1% in the fondaparinux group, he said.

Rivaroxaban reduced the relative risk of the composite of proximal DVT, pulmonary embolism, and VTE-related death by 29%, compared with LMWH, and 42% compared with fondaparinux, but the difference between the three groups did not achieve statistical significance (1.0% vs. 1.4% vs. 1.7%), Dr. Beyer-Westendorf said.

In a pooled analysis of RECORD 1, 2, and 3, rivaroxaban significantly reduced the composite of symptomatic VTE and all-cause mortality during the 2-week period after surgery, compared with enoxaparin (0.4% vs. 0.8%), according to the Bayer HealthCare website.

In the current analysis, severe bleeding was significantly lower with rivaroxaban at 7.4% vs. 14.9% with LMWH, and 11.1% with fondaparinux.

Bleeding leading to surgical revisions was also significantly lower at 0.4% vs. 1.7% with LMWH, and 1.1% with fondaparinux.

Dr. Beyer-Westendorf pointed out that severe bleeding rates were less than 1% in the RECORD 1-4 trials using a more narrow definition of severe bleeding as overt bleeding outside of the surgical site. Their analysis used the International Society on Thrombosis and Hemostasis criteria for severe bleeding.

Finally, the reduction in VTE events, bleeding, and surgical revisions was correlated with a significantly shorter median hospital stay in patients given rivaroxaban prophylaxis vs. LMWH or fondaparinux (8.3 days vs. 11.6 days vs. 9.3 days).

Dr. Beyer-Westendorf said it was unlikely that changes in anesthesia or surgical practice over the study period could have attenuated the results. In addition, the researchers conducted a matched-pair analysis to evaluate whether the benefits of rivaroxaban were due to selection or detection bias. Outcomes remained superior for rivaroxaban after matching patients according to age, gender, type of surgery, and history of VTE. Complete compression ultrasound testing also remained constant at about 13% from 2005 to 2010 before falling to 8.2% in 2011 due to fewer complete compression ultrasound–positive findings, Dr. Beyer-Westendorf noted.

"These findings in a large real-world surgery cohort are robust and not significantly influenced by a selection or detection bias," he said.

Dr. Beyer-Westendorf disclosed research grants from and serving as a speaker for Bayer HealthCare, which markets Xarelto.

SAN DIEGO – Prophylaxis with rivaroxaban achieved significant reductions in venous thromboembolism, compared with two commonly used drugs when put to the test in 5,346 consecutive, unselected patients undergoing major orthopedic surgery.

The incidence of in-hospital symptomatic venous thromboembolism (VTE) was 2.4% with rivaroxaban (Xarelto), compared with 3.9% with low molecular weight heparin (LMWH), and 5.5% with fondaparinux (Arixtra). This corresponds to a relative risk reduction of 39%, compared with LMWH, and 57% compared with fondaparinux.

Rivaroxaban, an oral Factor Xa inhibitor, also has superior safety with regard to major bleeding and surgical complications, according to Dr. Jan Beyer-Westendorf, with the University Clinic at Dresden (Germany) Technical University.

"Patients in real-world major orthopedic surgery benefit from VTE-prophylaxis with rivaroxaban even more than could be expected from the phase III results of the RECORD trial," he said at the annual meeting of the American Society of Hematology.

The four phase III RECORD (REgulation of Coagulation in ORthopedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism) trials compared rivaroxaban with enoxaparin in more than 12,500 patients undergoing knee and hip replacement. The trials did not evaluate fondaparinux or LMWH, despite being the standard of care at many hospitals.

Rivaroxaban was approved in the United States in July 2011 for DVT prophylaxis in adults undergoing hip and knee replacement surgery, and gained a second indication in November 2011 for stroke prophylaxis in patients with nonvalvular atrial fibrillation.

Dr. Beyer-Westendorf and his colleagues analyzed 5,346 consecutive patients who underwent major orthopedic surgery at the university clinic during three periods: 2005-2007 when LMWH was the standard prophylaxis; 2008-2009 when fondaparinux was the standard; and finally from 2010 to June 2011 when rivaroxaban became the clinic’s standard prophylaxis.

In all, 1,055 patients were treated with rivaroxaban, 1,683 with LMWH, and 2,069 with fondaparinux. Of note, previous VTE was more common at baseline in the rivaroxaban group at 4% vs. 1.4% in the LMWH group, and 1.1% in the fondaparinux group, he said.

Rivaroxaban reduced the relative risk of the composite of proximal DVT, pulmonary embolism, and VTE-related death by 29%, compared with LMWH, and 42% compared with fondaparinux, but the difference between the three groups did not achieve statistical significance (1.0% vs. 1.4% vs. 1.7%), Dr. Beyer-Westendorf said.

In a pooled analysis of RECORD 1, 2, and 3, rivaroxaban significantly reduced the composite of symptomatic VTE and all-cause mortality during the 2-week period after surgery, compared with enoxaparin (0.4% vs. 0.8%), according to the Bayer HealthCare website.

In the current analysis, severe bleeding was significantly lower with rivaroxaban at 7.4% vs. 14.9% with LMWH, and 11.1% with fondaparinux.

Bleeding leading to surgical revisions was also significantly lower at 0.4% vs. 1.7% with LMWH, and 1.1% with fondaparinux.

Dr. Beyer-Westendorf pointed out that severe bleeding rates were less than 1% in the RECORD 1-4 trials using a more narrow definition of severe bleeding as overt bleeding outside of the surgical site. Their analysis used the International Society on Thrombosis and Hemostasis criteria for severe bleeding.

Finally, the reduction in VTE events, bleeding, and surgical revisions was correlated with a significantly shorter median hospital stay in patients given rivaroxaban prophylaxis vs. LMWH or fondaparinux (8.3 days vs. 11.6 days vs. 9.3 days).

Dr. Beyer-Westendorf said it was unlikely that changes in anesthesia or surgical practice over the study period could have attenuated the results. In addition, the researchers conducted a matched-pair analysis to evaluate whether the benefits of rivaroxaban were due to selection or detection bias. Outcomes remained superior for rivaroxaban after matching patients according to age, gender, type of surgery, and history of VTE. Complete compression ultrasound testing also remained constant at about 13% from 2005 to 2010 before falling to 8.2% in 2011 due to fewer complete compression ultrasound–positive findings, Dr. Beyer-Westendorf noted.

"These findings in a large real-world surgery cohort are robust and not significantly influenced by a selection or detection bias," he said.

Dr. Beyer-Westendorf disclosed research grants from and serving as a speaker for Bayer HealthCare, which markets Xarelto.

Nearly half of North American police officers might be suffering from a sleep disorder that could interfere with the safe execution of their duties.

A survey of nearly 5,000 officers found that 40.4% of them screened positive for a sleep disorder, most of these undiagnosed. Those officers with a sleep disorder were significantly more likely to commit administrative errors, lose their temper with citizens, and even fall asleep while driving, Shantha M.W. Rajaratnam, Ph.D., and colleagues reported in the Dec. 21 issue of JAMA.

Photo: Antonprado/iStock.com

"Almost half [reported] having fallen asleep while driving" and about one-quarter said that this occurs one to two times per month, said Dr. Rajaratnam of Brigham and Women’s Hospital, Boston. "This is despite police officers apparently recognizing the dangers associated with drowsy driving." In a different survey of North American police officers, almost 90% regarded drowsy driving to be as dangerous as drunk driving, the investigators noted (JAMA 2011;306:2567-78).

The team conducted an online and in-person survey of 4,957 police officers, 97% of whom were based in the United States and 3% in Canada. The subjects responded to a variety of questionnaires that screen for sleep disorders, including obstructive sleep apnea, insomnia, restless legs syndrome, narcolepsy, and cataplexy. The survey also screened for shift-work disorder. Subjects provided basic health information, as well as information about alcohol intake and feelings of emotional burnout. They then completed monthly surveys for the next 2 years, with an accumulation of 15, 735 surveys.

The mean age of the cohort was 38.5 years; 82.3% were male. More than half (58%) reported their health as very good or excellent. However, 79.3% of the respondents were overweight or obese, and 33.5% were obese.

Most were patrol officers (66.5%), followed by managers (15%), criminal investigators (8.2%), and other job positions. Only 38% reported never having night-shift work; the rest worked overnight from once per month to nearly every shift.

Of the entire cohort, 2,003 (40.4%) screened positive for at least one sleep disorder. Obstructive sleep apnea was the most commonly identified problem, affecting 1,666 (33.6%) of the subjects. The next most commonly identified problem was moderate to severe insomnia, found in 281 (6.5%).

Other findings were shift-work disorder (269), restless legs syndrome (70), and narcolepsy with cataplexy (16).

The group with shift-work disorder represented 14% of those who worked overnight hours, the investigators noted. However, they said, if they applied the International Classification of Sleep Disorders–2 criteria for shift work disorder (excessive wake-time sleepiness or insomnia), then 1,004 (53.9%) of the police officers who worked night shifts screened positive.

The investigators found some significant associations between sleep disorders and health/safety outcomes. Those with a positive screen were almost three times as likely to report depression (odds ratio, 2.75) and emotional job burnout (OR, 2.87), and almost five times as likely to report having fallen asleep while driving after work (OR, 4.64). Of the entire cohort, 2,276 (46%) reported having fallen asleep while driving (56.9% at least once a month, and 13.5% once or twice a week).

At the 2-year follow-up, data were collected on 6,587 person-months for those with positive screens and 9,148 person-months for those with negative screens. Again, the authors found significant correlations between a sleep disorder and a behavioral or safety issue. Compared with those having a negative screen, those with a positive screen were 43% more likely to make an administrative error, 51% more likely to fall asleep while driving, and 63% more likely to make a fatigue-related safety error.

Sleep disorders also significantly correlated with public interaction. Those with positive screens were 25% more likely to experience uncontrolled anger at a citizen or suspect, and 35% more likely to incur a citizen complaint.

Over the follow-up period, those in the cohort experienced 287 motor vehicle accidents, which were 49% more common among those who had reported falling asleep while driving and 68% more common among those who reported falling asleep while stopped in traffic.

Dr. Rajaratnam reported numerous financial relationships with pharmaceutical and medical device companies. The study was sponsored by National Institute of Justice and the Centers for Disease Control and Prevention.

Nearly half of North American police officers might be suffering from a sleep disorder that could interfere with the safe execution of their duties.

A survey of nearly 5,000 officers found that 40.4% of them screened positive for a sleep disorder, most of these undiagnosed. Those officers with a sleep disorder were significantly more likely to commit administrative errors, lose their temper with citizens, and even fall asleep while driving, Shantha M.W. Rajaratnam, Ph.D., and colleagues reported in the Dec. 21 issue of JAMA.

Photo: Antonprado/iStock.com

"Almost half [reported] having fallen asleep while driving" and about one-quarter said that this occurs one to two times per month, said Dr. Rajaratnam of Brigham and Women’s Hospital, Boston. "This is despite police officers apparently recognizing the dangers associated with drowsy driving." In a different survey of North American police officers, almost 90% regarded drowsy driving to be as dangerous as drunk driving, the investigators noted (JAMA 2011;306:2567-78).

The team conducted an online and in-person survey of 4,957 police officers, 97% of whom were based in the United States and 3% in Canada. The subjects responded to a variety of questionnaires that screen for sleep disorders, including obstructive sleep apnea, insomnia, restless legs syndrome, narcolepsy, and cataplexy. The survey also screened for shift-work disorder. Subjects provided basic health information, as well as information about alcohol intake and feelings of emotional burnout. They then completed monthly surveys for the next 2 years, with an accumulation of 15, 735 surveys.

The mean age of the cohort was 38.5 years; 82.3% were male. More than half (58%) reported their health as very good or excellent. However, 79.3% of the respondents were overweight or obese, and 33.5% were obese.

Most were patrol officers (66.5%), followed by managers (15%), criminal investigators (8.2%), and other job positions. Only 38% reported never having night-shift work; the rest worked overnight from once per month to nearly every shift.

Of the entire cohort, 2,003 (40.4%) screened positive for at least one sleep disorder. Obstructive sleep apnea was the most commonly identified problem, affecting 1,666 (33.6%) of the subjects. The next most commonly identified problem was moderate to severe insomnia, found in 281 (6.5%).

Other findings were shift-work disorder (269), restless legs syndrome (70), and narcolepsy with cataplexy (16).

The group with shift-work disorder represented 14% of those who worked overnight hours, the investigators noted. However, they said, if they applied the International Classification of Sleep Disorders–2 criteria for shift work disorder (excessive wake-time sleepiness or insomnia), then 1,004 (53.9%) of the police officers who worked night shifts screened positive.

The investigators found some significant associations between sleep disorders and health/safety outcomes. Those with a positive screen were almost three times as likely to report depression (odds ratio, 2.75) and emotional job burnout (OR, 2.87), and almost five times as likely to report having fallen asleep while driving after work (OR, 4.64). Of the entire cohort, 2,276 (46%) reported having fallen asleep while driving (56.9% at least once a month, and 13.5% once or twice a week).

At the 2-year follow-up, data were collected on 6,587 person-months for those with positive screens and 9,148 person-months for those with negative screens. Again, the authors found significant correlations between a sleep disorder and a behavioral or safety issue. Compared with those having a negative screen, those with a positive screen were 43% more likely to make an administrative error, 51% more likely to fall asleep while driving, and 63% more likely to make a fatigue-related safety error.

Sleep disorders also significantly correlated with public interaction. Those with positive screens were 25% more likely to experience uncontrolled anger at a citizen or suspect, and 35% more likely to incur a citizen complaint.

Over the follow-up period, those in the cohort experienced 287 motor vehicle accidents, which were 49% more common among those who had reported falling asleep while driving and 68% more common among those who reported falling asleep while stopped in traffic.

Dr. Rajaratnam reported numerous financial relationships with pharmaceutical and medical device companies. The study was sponsored by National Institute of Justice and the Centers for Disease Control and Prevention.

Nearly half of North American police officers might be suffering from a sleep disorder that could interfere with the safe execution of their duties.

A survey of nearly 5,000 officers found that 40.4% of them screened positive for a sleep disorder, most of these undiagnosed. Those officers with a sleep disorder were significantly more likely to commit administrative errors, lose their temper with citizens, and even fall asleep while driving, Shantha M.W. Rajaratnam, Ph.D., and colleagues reported in the Dec. 21 issue of JAMA.

Photo: Antonprado/iStock.com

"Almost half [reported] having fallen asleep while driving" and about one-quarter said that this occurs one to two times per month, said Dr. Rajaratnam of Brigham and Women’s Hospital, Boston. "This is despite police officers apparently recognizing the dangers associated with drowsy driving." In a different survey of North American police officers, almost 90% regarded drowsy driving to be as dangerous as drunk driving, the investigators noted (JAMA 2011;306:2567-78).

The team conducted an online and in-person survey of 4,957 police officers, 97% of whom were based in the United States and 3% in Canada. The subjects responded to a variety of questionnaires that screen for sleep disorders, including obstructive sleep apnea, insomnia, restless legs syndrome, narcolepsy, and cataplexy. The survey also screened for shift-work disorder. Subjects provided basic health information, as well as information about alcohol intake and feelings of emotional burnout. They then completed monthly surveys for the next 2 years, with an accumulation of 15, 735 surveys.

The mean age of the cohort was 38.5 years; 82.3% were male. More than half (58%) reported their health as very good or excellent. However, 79.3% of the respondents were overweight or obese, and 33.5% were obese.

Most were patrol officers (66.5%), followed by managers (15%), criminal investigators (8.2%), and other job positions. Only 38% reported never having night-shift work; the rest worked overnight from once per month to nearly every shift.

Of the entire cohort, 2,003 (40.4%) screened positive for at least one sleep disorder. Obstructive sleep apnea was the most commonly identified problem, affecting 1,666 (33.6%) of the subjects. The next most commonly identified problem was moderate to severe insomnia, found in 281 (6.5%).

Other findings were shift-work disorder (269), restless legs syndrome (70), and narcolepsy with cataplexy (16).

The group with shift-work disorder represented 14% of those who worked overnight hours, the investigators noted. However, they said, if they applied the International Classification of Sleep Disorders–2 criteria for shift work disorder (excessive wake-time sleepiness or insomnia), then 1,004 (53.9%) of the police officers who worked night shifts screened positive.

The investigators found some significant associations between sleep disorders and health/safety outcomes. Those with a positive screen were almost three times as likely to report depression (odds ratio, 2.75) and emotional job burnout (OR, 2.87), and almost five times as likely to report having fallen asleep while driving after work (OR, 4.64). Of the entire cohort, 2,276 (46%) reported having fallen asleep while driving (56.9% at least once a month, and 13.5% once or twice a week).

At the 2-year follow-up, data were collected on 6,587 person-months for those with positive screens and 9,148 person-months for those with negative screens. Again, the authors found significant correlations between a sleep disorder and a behavioral or safety issue. Compared with those having a negative screen, those with a positive screen were 43% more likely to make an administrative error, 51% more likely to fall asleep while driving, and 63% more likely to make a fatigue-related safety error.

Sleep disorders also significantly correlated with public interaction. Those with positive screens were 25% more likely to experience uncontrolled anger at a citizen or suspect, and 35% more likely to incur a citizen complaint.

Over the follow-up period, those in the cohort experienced 287 motor vehicle accidents, which were 49% more common among those who had reported falling asleep while driving and 68% more common among those who reported falling asleep while stopped in traffic.

Dr. Rajaratnam reported numerous financial relationships with pharmaceutical and medical device companies. The study was sponsored by National Institute of Justice and the Centers for Disease Control and Prevention.

Survivors of acute lung injury are likely to experience depression and physical impairment for up to 2 years after leaving the intensive care unit.

In a prospective study, 40% of patients had new-onset depression and 66% had new physical impairment after discharge. The findings seem inextricably linked on both psychological and physiological levels, Dr. Oscar J. Bienvenu and his colleagues wrote in the American Journal of Respiratory and Critical Care Medicine.

"Depressive symptoms may decrease motivation for and reward from the physical activities necessary for recovery of maintenance of functioning ... [they] can also amplify symptoms of general medical illnesses, and an increased physical symptom load could negatively affect functioning."

In addition, there may be less-understood links between depression and physical functioning, wrote Dr. Bienvenu of Johns Hopkins University, Baltimore, and his coauthors.

"Depressive symptoms could affect functioning through direct neurobiologic pathways, including neuroendocrine and inflammatory mechanisms."

The study comprised 2-year follow-up data on 186 patients. All of the patients were mechanically ventilated for acute lung injury (ALI). Baseline depression was present in 21% and baseline physical impairment in 40% (Am. J. Respir. Crit. Care Med. 2011 Dec. 8 [doi:10.1164/rccm.201103-0503OC]).

The patients’ mean age was 49 years; 56% were male. The mean length of stay in the intensive care unit (ICU) was 19 days. Patients were assessed for depression and physical function at 3, 6, 12, and 14 months after discharge.

During the entire follow-up period, 40% of the patients experienced new-onset depression and 66% had new-onset physical impairment. Remission occurred in 39% of those with depression and 54% of those with physical impairment, but there was recurrence in 20% and 14%, respectively. Most of those who developed depression or physical impairment had symptoms at 24 months (69% and 58%).

Patients who did remit, however, tended to do well. In those with remitted depression, the mean score on the Hospital and Anxiety Depression Scale remained about 5, indicating normal mood. In those whose symptoms did not remit, the score remained 10 or higher, indicating moderate to severe depression.

Similarly, those with remission of physical impairment had a mean of 1 impaired activity of daily living, compared with a mean of 4 or more in those with unremitted impairments.

When the authors looked at potential risk factors for new-onset depression and physical impairment, only two remained statistically significant in multivariate analyses. Education of 12 or fewer years increased the risk of new-onset depression by more than three times. Only depression at last follow-up significantly correlated with new-onset physical impairment (odds ratio, 2.7)

"Our analyses indicate that depressive symptoms are not only relatively persistent in ALI survivors, they are also an independent risk factor for subsequent impairment in physical function," the authors wrote. "Hence, early identification and treatment of depressive states should be evaluated as a potential intervention to minimize the suffering and impairment that affect too many of these patients."

The National Institutes of Health supported the study. None of the authors reported any financial conflicts.

Survivors of acute lung injury are likely to experience depression and physical impairment for up to 2 years after leaving the intensive care unit.

In a prospective study, 40% of patients had new-onset depression and 66% had new physical impairment after discharge. The findings seem inextricably linked on both psychological and physiological levels, Dr. Oscar J. Bienvenu and his colleagues wrote in the American Journal of Respiratory and Critical Care Medicine.

"Depressive symptoms may decrease motivation for and reward from the physical activities necessary for recovery of maintenance of functioning ... [they] can also amplify symptoms of general medical illnesses, and an increased physical symptom load could negatively affect functioning."

In addition, there may be less-understood links between depression and physical functioning, wrote Dr. Bienvenu of Johns Hopkins University, Baltimore, and his coauthors.

"Depressive symptoms could affect functioning through direct neurobiologic pathways, including neuroendocrine and inflammatory mechanisms."

The study comprised 2-year follow-up data on 186 patients. All of the patients were mechanically ventilated for acute lung injury (ALI). Baseline depression was present in 21% and baseline physical impairment in 40% (Am. J. Respir. Crit. Care Med. 2011 Dec. 8 [doi:10.1164/rccm.201103-0503OC]).

The patients’ mean age was 49 years; 56% were male. The mean length of stay in the intensive care unit (ICU) was 19 days. Patients were assessed for depression and physical function at 3, 6, 12, and 14 months after discharge.

During the entire follow-up period, 40% of the patients experienced new-onset depression and 66% had new-onset physical impairment. Remission occurred in 39% of those with depression and 54% of those with physical impairment, but there was recurrence in 20% and 14%, respectively. Most of those who developed depression or physical impairment had symptoms at 24 months (69% and 58%).

Patients who did remit, however, tended to do well. In those with remitted depression, the mean score on the Hospital and Anxiety Depression Scale remained about 5, indicating normal mood. In those whose symptoms did not remit, the score remained 10 or higher, indicating moderate to severe depression.

Similarly, those with remission of physical impairment had a mean of 1 impaired activity of daily living, compared with a mean of 4 or more in those with unremitted impairments.

When the authors looked at potential risk factors for new-onset depression and physical impairment, only two remained statistically significant in multivariate analyses. Education of 12 or fewer years increased the risk of new-onset depression by more than three times. Only depression at last follow-up significantly correlated with new-onset physical impairment (odds ratio, 2.7)

"Our analyses indicate that depressive symptoms are not only relatively persistent in ALI survivors, they are also an independent risk factor for subsequent impairment in physical function," the authors wrote. "Hence, early identification and treatment of depressive states should be evaluated as a potential intervention to minimize the suffering and impairment that affect too many of these patients."

The National Institutes of Health supported the study. None of the authors reported any financial conflicts.

Survivors of acute lung injury are likely to experience depression and physical impairment for up to 2 years after leaving the intensive care unit.

In a prospective study, 40% of patients had new-onset depression and 66% had new physical impairment after discharge. The findings seem inextricably linked on both psychological and physiological levels, Dr. Oscar J. Bienvenu and his colleagues wrote in the American Journal of Respiratory and Critical Care Medicine.

"Depressive symptoms may decrease motivation for and reward from the physical activities necessary for recovery of maintenance of functioning ... [they] can also amplify symptoms of general medical illnesses, and an increased physical symptom load could negatively affect functioning."

In addition, there may be less-understood links between depression and physical functioning, wrote Dr. Bienvenu of Johns Hopkins University, Baltimore, and his coauthors.

"Depressive symptoms could affect functioning through direct neurobiologic pathways, including neuroendocrine and inflammatory mechanisms."

The study comprised 2-year follow-up data on 186 patients. All of the patients were mechanically ventilated for acute lung injury (ALI). Baseline depression was present in 21% and baseline physical impairment in 40% (Am. J. Respir. Crit. Care Med. 2011 Dec. 8 [doi:10.1164/rccm.201103-0503OC]).

The patients’ mean age was 49 years; 56% were male. The mean length of stay in the intensive care unit (ICU) was 19 days. Patients were assessed for depression and physical function at 3, 6, 12, and 14 months after discharge.

During the entire follow-up period, 40% of the patients experienced new-onset depression and 66% had new-onset physical impairment. Remission occurred in 39% of those with depression and 54% of those with physical impairment, but there was recurrence in 20% and 14%, respectively. Most of those who developed depression or physical impairment had symptoms at 24 months (69% and 58%).

Patients who did remit, however, tended to do well. In those with remitted depression, the mean score on the Hospital and Anxiety Depression Scale remained about 5, indicating normal mood. In those whose symptoms did not remit, the score remained 10 or higher, indicating moderate to severe depression.

Similarly, those with remission of physical impairment had a mean of 1 impaired activity of daily living, compared with a mean of 4 or more in those with unremitted impairments.

When the authors looked at potential risk factors for new-onset depression and physical impairment, only two remained statistically significant in multivariate analyses. Education of 12 or fewer years increased the risk of new-onset depression by more than three times. Only depression at last follow-up significantly correlated with new-onset physical impairment (odds ratio, 2.7)

"Our analyses indicate that depressive symptoms are not only relatively persistent in ALI survivors, they are also an independent risk factor for subsequent impairment in physical function," the authors wrote. "Hence, early identification and treatment of depressive states should be evaluated as a potential intervention to minimize the suffering and impairment that affect too many of these patients."

The National Institutes of Health supported the study. None of the authors reported any financial conflicts.

A device that provides cooled, filtered airflow while patients sleep improved quality of life in patients with atopic asthma, according to the findings of randomized controlled trial conducted in six European countries.

The benefits of treatment with the device, Protexo, developed by Airsonett, seemed "greatest in patients with a combination of high asthma intensity and poor asthma control, who represent a significant area of unmet need," said Dr. Robert J. Boyle of the pediatrics department at Imperial College London, and his coinvestigators.

A total of 312 patients with atopic asthma were randomized to use the device, which filters and cools the air near the user’s nighttime breathing zone, or an identical placebo device. The active therapy arm received temperature-controlled laminar airflow (TLA) treatment, which is proposed to decrease exposure to allergens.

The primary end point of the phase III study was an improvement of at least 0.5 points on the Asthma Quality of Life Questionnaire. Secondary end points included fractional exhaled nitric oxide (FENO); IgE levels and blood eosinophil count; and airflow obstruction as measured by forced expiratory volume in 1 second (FEV₁), forced expiratory flow at 50% of vital capacity (FEF₅₀), and peak expiratory flow (PEF). Subgroup analyses were done by age, treatment intensity at baseline, symptom control at baseline, and a combination of treatment intensity and symptom control (Thorax 2011 [doi:10.1136/thoraxjnl-2011-200665).

Participants were enrolled between April 2008 and February 2009, and the two groups had similar demographic and clinical characteristics at baseline. Patients were aged 7-70 years (mean 24 years), had a history of asthma for at least 1 year (mean approximately 13 years), had a demonstrated allergy to pets or dust mites, and were on daily corticosteroids. A little over half of the participants were male. Patients continued using asthma medications as needed during the study and underwent medical assessment at 1, 3, 6, 9 and 12 months.

Of the active treatment group, 76% reached the primary end point at 1 year, compared with 61% of the placebo group, a significant difference (95% confidence interval 3%-27%, P = .02). Findings were similar for the subgroup analysis of patients aged 12 years and older (74% vs. 60%; 95% CI 1%-28%, P = .06). The greatest difference was seen in TLA recipients who had both high treatment intensity and low symptom control at baseline, compared with similar patients who received placebo (75% vs. 50%; 95% CI 4%-47%, P = .009).

Regarding the secondary outcomes, use of the treatment device was linked to a greater decrease in FENO, with a mean difference of –7.1 parts per billion, compared with use of the placebo device (95% CI –13.6 to –0.7, P = .03). The treatment group also saw a smaller increase in cat-specific IgE levels relative to baseline, compared with the placebo group (8% vs. 35%), and smaller increases in IgE levels specific to dust mites and dog allergens (differences not significant). No significant differences were found between groups in total IgE level change, eosinophil count, FEV₁, FEF₅₀, or PEF. There also were no differences in medication use or exacerbation rates.

Although previous studies have found no benefit to avoiding allergens in asthma, this study "found that exposure control using TLA treatment at night has an impact on overall asthma-related quality of life," Dr. Boyle and his colleagues wrote. The researchers theorized that "the reason that nocturnal TLA is successful where so many other approaches have failed may be the profound reduction in inhaled aeroallergen exposure." They suggested that "the clinical effects of TLA can be explained by its ability to break the persistent body convection and thereby reduce aeroallergen exposure."

Because the patient cohort encompassed a wide range of ages and residents of several countries, the authors said that "the clinical effects of nocturnal TLA treatment appear to be applicable to a broad patient group." However, they noted that it may be of most benefit in "patients with uncontrolled atopic asthma despite high treatment intensity, where guidelines recommend stepping up treatment."

There were no treatment-related adverse events in either group.

The study was funded by Airsonett. The researchers reported having no other financial conflicts.

A device that provides cooled, filtered airflow while patients sleep improved quality of life in patients with atopic asthma, according to the findings of randomized controlled trial conducted in six European countries.

The benefits of treatment with the device, Protexo, developed by Airsonett, seemed "greatest in patients with a combination of high asthma intensity and poor asthma control, who represent a significant area of unmet need," said Dr. Robert J. Boyle of the pediatrics department at Imperial College London, and his coinvestigators.

A total of 312 patients with atopic asthma were randomized to use the device, which filters and cools the air near the user’s nighttime breathing zone, or an identical placebo device. The active therapy arm received temperature-controlled laminar airflow (TLA) treatment, which is proposed to decrease exposure to allergens.

The primary end point of the phase III study was an improvement of at least 0.5 points on the Asthma Quality of Life Questionnaire. Secondary end points included fractional exhaled nitric oxide (FENO); IgE levels and blood eosinophil count; and airflow obstruction as measured by forced expiratory volume in 1 second (FEV₁), forced expiratory flow at 50% of vital capacity (FEF₅₀), and peak expiratory flow (PEF). Subgroup analyses were done by age, treatment intensity at baseline, symptom control at baseline, and a combination of treatment intensity and symptom control (Thorax 2011 [doi:10.1136/thoraxjnl-2011-200665).

Participants were enrolled between April 2008 and February 2009, and the two groups had similar demographic and clinical characteristics at baseline. Patients were aged 7-70 years (mean 24 years), had a history of asthma for at least 1 year (mean approximately 13 years), had a demonstrated allergy to pets or dust mites, and were on daily corticosteroids. A little over half of the participants were male. Patients continued using asthma medications as needed during the study and underwent medical assessment at 1, 3, 6, 9 and 12 months.

Of the active treatment group, 76% reached the primary end point at 1 year, compared with 61% of the placebo group, a significant difference (95% confidence interval 3%-27%, P = .02). Findings were similar for the subgroup analysis of patients aged 12 years and older (74% vs. 60%; 95% CI 1%-28%, P = .06). The greatest difference was seen in TLA recipients who had both high treatment intensity and low symptom control at baseline, compared with similar patients who received placebo (75% vs. 50%; 95% CI 4%-47%, P = .009).

Regarding the secondary outcomes, use of the treatment device was linked to a greater decrease in FENO, with a mean difference of –7.1 parts per billion, compared with use of the placebo device (95% CI –13.6 to –0.7, P = .03). The treatment group also saw a smaller increase in cat-specific IgE levels relative to baseline, compared with the placebo group (8% vs. 35%), and smaller increases in IgE levels specific to dust mites and dog allergens (differences not significant). No significant differences were found between groups in total IgE level change, eosinophil count, FEV₁, FEF₅₀, or PEF. There also were no differences in medication use or exacerbation rates.

Although previous studies have found no benefit to avoiding allergens in asthma, this study "found that exposure control using TLA treatment at night has an impact on overall asthma-related quality of life," Dr. Boyle and his colleagues wrote. The researchers theorized that "the reason that nocturnal TLA is successful where so many other approaches have failed may be the profound reduction in inhaled aeroallergen exposure." They suggested that "the clinical effects of TLA can be explained by its ability to break the persistent body convection and thereby reduce aeroallergen exposure."

Because the patient cohort encompassed a wide range of ages and residents of several countries, the authors said that "the clinical effects of nocturnal TLA treatment appear to be applicable to a broad patient group." However, they noted that it may be of most benefit in "patients with uncontrolled atopic asthma despite high treatment intensity, where guidelines recommend stepping up treatment."

There were no treatment-related adverse events in either group.

The study was funded by Airsonett. The researchers reported having no other financial conflicts.

A device that provides cooled, filtered airflow while patients sleep improved quality of life in patients with atopic asthma, according to the findings of randomized controlled trial conducted in six European countries.

The benefits of treatment with the device, Protexo, developed by Airsonett, seemed "greatest in patients with a combination of high asthma intensity and poor asthma control, who represent a significant area of unmet need," said Dr. Robert J. Boyle of the pediatrics department at Imperial College London, and his coinvestigators.

A total of 312 patients with atopic asthma were randomized to use the device, which filters and cools the air near the user’s nighttime breathing zone, or an identical placebo device. The active therapy arm received temperature-controlled laminar airflow (TLA) treatment, which is proposed to decrease exposure to allergens.

The primary end point of the phase III study was an improvement of at least 0.5 points on the Asthma Quality of Life Questionnaire. Secondary end points included fractional exhaled nitric oxide (FENO); IgE levels and blood eosinophil count; and airflow obstruction as measured by forced expiratory volume in 1 second (FEV₁), forced expiratory flow at 50% of vital capacity (FEF₅₀), and peak expiratory flow (PEF). Subgroup analyses were done by age, treatment intensity at baseline, symptom control at baseline, and a combination of treatment intensity and symptom control (Thorax 2011 [doi:10.1136/thoraxjnl-2011-200665).

Participants were enrolled between April 2008 and February 2009, and the two groups had similar demographic and clinical characteristics at baseline. Patients were aged 7-70 years (mean 24 years), had a history of asthma for at least 1 year (mean approximately 13 years), had a demonstrated allergy to pets or dust mites, and were on daily corticosteroids. A little over half of the participants were male. Patients continued using asthma medications as needed during the study and underwent medical assessment at 1, 3, 6, 9 and 12 months.

Of the active treatment group, 76% reached the primary end point at 1 year, compared with 61% of the placebo group, a significant difference (95% confidence interval 3%-27%, P = .02). Findings were similar for the subgroup analysis of patients aged 12 years and older (74% vs. 60%; 95% CI 1%-28%, P = .06). The greatest difference was seen in TLA recipients who had both high treatment intensity and low symptom control at baseline, compared with similar patients who received placebo (75% vs. 50%; 95% CI 4%-47%, P = .009).

Regarding the secondary outcomes, use of the treatment device was linked to a greater decrease in FENO, with a mean difference of –7.1 parts per billion, compared with use of the placebo device (95% CI –13.6 to –0.7, P = .03). The treatment group also saw a smaller increase in cat-specific IgE levels relative to baseline, compared with the placebo group (8% vs. 35%), and smaller increases in IgE levels specific to dust mites and dog allergens (differences not significant). No significant differences were found between groups in total IgE level change, eosinophil count, FEV₁, FEF₅₀, or PEF. There also were no differences in medication use or exacerbation rates.

Although previous studies have found no benefit to avoiding allergens in asthma, this study "found that exposure control using TLA treatment at night has an impact on overall asthma-related quality of life," Dr. Boyle and his colleagues wrote. The researchers theorized that "the reason that nocturnal TLA is successful where so many other approaches have failed may be the profound reduction in inhaled aeroallergen exposure." They suggested that "the clinical effects of TLA can be explained by its ability to break the persistent body convection and thereby reduce aeroallergen exposure."

Because the patient cohort encompassed a wide range of ages and residents of several countries, the authors said that "the clinical effects of nocturnal TLA treatment appear to be applicable to a broad patient group." However, they noted that it may be of most benefit in "patients with uncontrolled atopic asthma despite high treatment intensity, where guidelines recommend stepping up treatment."

There were no treatment-related adverse events in either group.

The study was funded by Airsonett. The researchers reported having no other financial conflicts.

Modified-risk tobacco products – such as e-cigarettes and tobacco lozenges that may reduce the health risks of using tobacco – could represent part of a comprehensive strategy to combat tobacco-related disease and death, but too little is known about whether they actually pose less risk than do traditional tobacco products, according to a report issued Dec. 14 by the Institute of Medicine.

Consequently, the Food and Drug Administration should require specific types of research on these modified-risk products before allowing tobacco companies to sell or advertise them as being capable of reducing the health effects of tobacco use, the IOM report recommended.

Photo courtesy timur1970/Fotolia.comCredit

The research should determine whether the product really presents a lessened risk for a person who might use it, Dr. Jane Henney, committee chair and professor of medicine and public health sciences at the University of Cincinnati, said in an interview. The product "also should not negatively impact the general public, as in the case of secondhand smoke, and it shouldn’t raise the risk" for nonusers or former users to begin or resume using the product.

Few smokers – only about 6% each year – are able to successfully quit tobacco use. Because quitting is so difficult, many cigarette smokers would welcome products that allow them to continue smoking with less risk to their health. However, there’s no research showing that modified-risk tobacco products are safer; in fact, so-called "light" cigarettes actually turned out to be just as risky as regular cigarettes, the IOM report said.

The Family Smoking Prevention and Control Act of 2009 gave the FDA the authority to ensure that modified-risk tobacco products actually do reduce tobacco-related harm before they can be marketed. The 2009 law also directed the IOM to work with the FDA on the design and conduct of scientific studies of modified-risk tobacco products.

The 330-page report provides details on how such studies should be conducted.

The tobacco industry "is new to regulation, and has a past history that would lead one to believe it can’t be trustworthy," Dr. Henney said. "We speak to the governance tools that should be put in place to really open up this process."

In part because of this trust gap, companies and other sponsors who develop modified-risk tobacco products should consider using FDA-approved, independent third parties to oversee health and safety research on their product, the report recommended. Independent oversight would ensure that the data submitted to the FDA are reliable and credible, the report said, and it might help to lure institutions and scientists back into the field; currently, many refuse to conduct or publish research supported by the tobacco industry.

Tobacco makers currently lack the capacity and expertise to conduct valid scientific research on their own products, according to the IOM report.

The report recommends that studies on modified-risk tobacco products should examine the product’s composition and addiction potential, the amount of human exposure to harmful components, perceptions about the product’s effects and likelihood of addiction, and its effects on human health. Studies should be "generalizable" to the whole population, but also should include populations of special relevance, including current and former smokers, beginning smokers, adolescents, and populations at high risk for tobacco use.

IOM committee member Dr. Bonnie Halpern-Felsher, professor of pediatrics at the University of California, San Francisco, said in an interview that it’s especially critical to understand how these modified-risk products could impact adolescents.

"We do know that the majority of people who start smoking are adolescents," Dr. Halpern-Felsher said. "We need to make sure when these studies are done that they do include the adolescent population, and cover the health effects on adolescents and adolescents’ perceptions of the product and their likelihood of going on to use it."

No disclosures were reported.

Modified-risk tobacco products – such as e-cigarettes and tobacco lozenges that may reduce the health risks of using tobacco – could represent part of a comprehensive strategy to combat tobacco-related disease and death, but too little is known about whether they actually pose less risk than do traditional tobacco products, according to a report issued Dec. 14 by the Institute of Medicine.

Consequently, the Food and Drug Administration should require specific types of research on these modified-risk products before allowing tobacco companies to sell or advertise them as being capable of reducing the health effects of tobacco use, the IOM report recommended.

Photo courtesy timur1970/Fotolia.comCredit

The research should determine whether the product really presents a lessened risk for a person who might use it, Dr. Jane Henney, committee chair and professor of medicine and public health sciences at the University of Cincinnati, said in an interview. The product "also should not negatively impact the general public, as in the case of secondhand smoke, and it shouldn’t raise the risk" for nonusers or former users to begin or resume using the product.

Few smokers – only about 6% each year – are able to successfully quit tobacco use. Because quitting is so difficult, many cigarette smokers would welcome products that allow them to continue smoking with less risk to their health. However, there’s no research showing that modified-risk tobacco products are safer; in fact, so-called "light" cigarettes actually turned out to be just as risky as regular cigarettes, the IOM report said.

The Family Smoking Prevention and Control Act of 2009 gave the FDA the authority to ensure that modified-risk tobacco products actually do reduce tobacco-related harm before they can be marketed. The 2009 law also directed the IOM to work with the FDA on the design and conduct of scientific studies of modified-risk tobacco products.

The 330-page report provides details on how such studies should be conducted.

The tobacco industry "is new to regulation, and has a past history that would lead one to believe it can’t be trustworthy," Dr. Henney said. "We speak to the governance tools that should be put in place to really open up this process."

In part because of this trust gap, companies and other sponsors who develop modified-risk tobacco products should consider using FDA-approved, independent third parties to oversee health and safety research on their product, the report recommended. Independent oversight would ensure that the data submitted to the FDA are reliable and credible, the report said, and it might help to lure institutions and scientists back into the field; currently, many refuse to conduct or publish research supported by the tobacco industry.

Tobacco makers currently lack the capacity and expertise to conduct valid scientific research on their own products, according to the IOM report.

The report recommends that studies on modified-risk tobacco products should examine the product’s composition and addiction potential, the amount of human exposure to harmful components, perceptions about the product’s effects and likelihood of addiction, and its effects on human health. Studies should be "generalizable" to the whole population, but also should include populations of special relevance, including current and former smokers, beginning smokers, adolescents, and populations at high risk for tobacco use.

IOM committee member Dr. Bonnie Halpern-Felsher, professor of pediatrics at the University of California, San Francisco, said in an interview that it’s especially critical to understand how these modified-risk products could impact adolescents.

"We do know that the majority of people who start smoking are adolescents," Dr. Halpern-Felsher said. "We need to make sure when these studies are done that they do include the adolescent population, and cover the health effects on adolescents and adolescents’ perceptions of the product and their likelihood of going on to use it."

No disclosures were reported.

Modified-risk tobacco products – such as e-cigarettes and tobacco lozenges that may reduce the health risks of using tobacco – could represent part of a comprehensive strategy to combat tobacco-related disease and death, but too little is known about whether they actually pose less risk than do traditional tobacco products, according to a report issued Dec. 14 by the Institute of Medicine.

Consequently, the Food and Drug Administration should require specific types of research on these modified-risk products before allowing tobacco companies to sell or advertise them as being capable of reducing the health effects of tobacco use, the IOM report recommended.

Photo courtesy timur1970/Fotolia.comCredit

The research should determine whether the product really presents a lessened risk for a person who might use it, Dr. Jane Henney, committee chair and professor of medicine and public health sciences at the University of Cincinnati, said in an interview. The product "also should not negatively impact the general public, as in the case of secondhand smoke, and it shouldn’t raise the risk" for nonusers or former users to begin or resume using the product.

Few smokers – only about 6% each year – are able to successfully quit tobacco use. Because quitting is so difficult, many cigarette smokers would welcome products that allow them to continue smoking with less risk to their health. However, there’s no research showing that modified-risk tobacco products are safer; in fact, so-called "light" cigarettes actually turned out to be just as risky as regular cigarettes, the IOM report said.

The Family Smoking Prevention and Control Act of 2009 gave the FDA the authority to ensure that modified-risk tobacco products actually do reduce tobacco-related harm before they can be marketed. The 2009 law also directed the IOM to work with the FDA on the design and conduct of scientific studies of modified-risk tobacco products.

The 330-page report provides details on how such studies should be conducted.

The tobacco industry "is new to regulation, and has a past history that would lead one to believe it can’t be trustworthy," Dr. Henney said. "We speak to the governance tools that should be put in place to really open up this process."

In part because of this trust gap, companies and other sponsors who develop modified-risk tobacco products should consider using FDA-approved, independent third parties to oversee health and safety research on their product, the report recommended. Independent oversight would ensure that the data submitted to the FDA are reliable and credible, the report said, and it might help to lure institutions and scientists back into the field; currently, many refuse to conduct or publish research supported by the tobacco industry.

Tobacco makers currently lack the capacity and expertise to conduct valid scientific research on their own products, according to the IOM report.

The report recommends that studies on modified-risk tobacco products should examine the product’s composition and addiction potential, the amount of human exposure to harmful components, perceptions about the product’s effects and likelihood of addiction, and its effects on human health. Studies should be "generalizable" to the whole population, but also should include populations of special relevance, including current and former smokers, beginning smokers, adolescents, and populations at high risk for tobacco use.

IOM committee member Dr. Bonnie Halpern-Felsher, professor of pediatrics at the University of California, San Francisco, said in an interview that it’s especially critical to understand how these modified-risk products could impact adolescents.

"We do know that the majority of people who start smoking are adolescents," Dr. Halpern-Felsher said. "We need to make sure when these studies are done that they do include the adolescent population, and cover the health effects on adolescents and adolescents’ perceptions of the product and their likelihood of going on to use it."

No disclosures were reported.

SAN FRANCISCO – Children in cardiopulmonary arrest require specialized resuscitation skills, and updated guidelines published late in 2010 contain some new recommendations, according to Dr. Marianne Gausche-Hill.

The recommended sequence for cardiopulmonary resuscitation (CPR) "has changed for all ages except for the newborn" to compressions, airway, breathing (CAB) – instead of airway, breathing, compressions (ABC) – when performed by a bystander. Emergency department (ED) providers usually will ventilate and do compressions simultaneously.

"If you’re doing bag mask [ventilation], the recommendation is just do your ventilations, and do compressions separately. If the patient has been intubated, you can do continued ventilations as you’re doing compressions," Dr. Gausche-Hill said at the annual meeting of the American College of Emergency Physicians.

In babies, if there is a single rescuer, chest compressions should be done using two fingers in the middle of the chest between the nipples (Circulation 2010;122:S862-75). With two rescuers, one can use the hand-encircling technique in which the thumbs are between the nipples and the rest of the fingers around the infant’s back, while the other does bag mask ventilation.

Compress the chest 1.5 inches in infants and 2 inches in children. Allow the chest to recoil between pushes and do at least 100 compressions per minute. "The key thing is to push hard and fast," said Dr. Gausche-Hill, professor of medicine at the University of California, Los Angeles. Do compressions for 2 minutes, then stop for no more than 10 seconds to check for a pulse. Mechanical devices for chest compressions have not been tested in children and should not be used in pediatric patients.

©2000 American Heart Association. Published by Elsevier Ireland Ltd. All rights reserved.

For a single rescuer, a ratio of compressions to ventilation of 30:2 is recommended, but for two rescuers in the ED the ratio is 15:2, with more emphasis on ventilation. Take care not to overventilate, she said.

"We overbag super amounts when we do resuscitation ventilation. You don’t need that much," she emphasized. "You want to squeeze the bag just until chest rise is initiated, and then begin the release phase." For children, this means about 10 breaths a minute. To avoid overbagging, a resuscitator can say "squeeze" as she squeezes the bag just until the chest starts to rise, then pause and say "release, release" to give time for the chest to recoil.

After beginning CPR, determine if the rhythm is shockable, and if so, use the defibrillator. Then do 2 minutes of CPR, give epinephrine, check the rhythm again, shock again. "It’s no more shock, shock, shock. You’re going to do 2 minutes of CPR in-between," she said.

The best option is a manual defibrillator with pediatric pads, she said, starting with 2 J and going up to 4 J if needed. But a dose even as high as 10 J is not harmful, according to Dr. Gausche-Hill. "If the patient is in persistent [ventricular fibrillation], I would strongly consider ramping it up, especially in the adolescent," she said. The new guidelines no longer require a pediatric attenuating device for an automated external defibrillator, and the standard automated external defibrillator can be used for any age (Circulation 2010;122:S876-908).

©2000 American Heart Association. Published by Elsevier Ireland Ltd. All rights reserved.

Cuffed endotracheal tubes (ETTs) are now preferred over the standard uncuffed tubes for intubation. "The bottom line is there’s no concern about cricoid pressure leading to necrosis. There’s no increased risk of subglottic stenosis by the use of these. That was really the main concern," she said. Cuffed ETTs are preferred in patients with poor lung compliance, a large glottic air leak, or high airway resistance. A randomized, controlled trial of 2,246 children found that those treated with a cuffed ETT did not have more postextubation stridor than those treated with an uncuffed ETT (4.4% vs. 4.7%) and were much less likely to need a tube exchange (2.1% vs. 30.8%) (Br. J. Anaesth. 2009;103:867-73). "Our PICU just says give it to everybody," she said. In pediatric patients, use a half-size smaller than their standard cuff size.

Cricoid pressure to present aspiration during intubation is not recommended in children, as it actually impedes the airway. Dr. Gausche-Hill prefers a jaw thrust or, in older kids, a little laryngeal manipulation.

In neonates, providing a lot of oxygen initially is harmful, leading to the creation of free radicals that may have an adverse neurologic effect (Circulation 2010;122:S909-19), but oxygen can be appropriate in older children, she said. "Bottom line is, give O₂ 100% and then back it down as quickly as you can," and aim to maintain an oxygen saturation of about 94%, said Dr. Gausche-Hill, who is also director of EMS and pediatric emergency medicine fellowships at Harbor-UCLA Medical Center in Torrance, Calif.

The guidelines now emphasize the use of capnography to monitor end-tidal CO₂ to confirm endotracheal tube placement and assess the adequacy of CPR. With capnography, "you may see [return of spontaneous circulation] before you can even detect a pulse," she said.

Foreign body aspiration "is your worst nightmare in the ED because you know if you can’t get it out, the patient’s going to die. And we do know that kids just do this all the time," she said. More than 90% of patients with this condition are younger than 5 years. "You always begin with basic life support maneuvers if they’re still conscious. For the infant, it’s back blows and chest thrusts until the object is expelled or they become unconscious." For the conscious older child, start with the Heimlich maneuver. In unconscious children, progress to chest compressions; if the foreign body is esophageal, chest compressions may remove it.

If the foreign body is lodged deeper in the airway, use direct laryngoscopy and remove the object with Magill forceps in the pediatric size. Some recent surveys showed that "18% of EDs in the country do not have pediatric Magills. Look in your airway kit. Make sure you have them," she stressed.

Last, family presence during resuscitation attempts should be promoted, she said. Almost a dozen studies have shown that parents want that option and should be included in decision making when possible, she noted.

Dr. Gausche-Hill reported having no significant financial relationships to disclose.

SAN FRANCISCO – Children in cardiopulmonary arrest require specialized resuscitation skills, and updated guidelines published late in 2010 contain some new recommendations, according to Dr. Marianne Gausche-Hill.

The recommended sequence for cardiopulmonary resuscitation (CPR) "has changed for all ages except for the newborn" to compressions, airway, breathing (CAB) – instead of airway, breathing, compressions (ABC) – when performed by a bystander. Emergency department (ED) providers usually will ventilate and do compressions simultaneously.

"If you’re doing bag mask [ventilation], the recommendation is just do your ventilations, and do compressions separately. If the patient has been intubated, you can do continued ventilations as you’re doing compressions," Dr. Gausche-Hill said at the annual meeting of the American College of Emergency Physicians.

In babies, if there is a single rescuer, chest compressions should be done using two fingers in the middle of the chest between the nipples (Circulation 2010;122:S862-75). With two rescuers, one can use the hand-encircling technique in which the thumbs are between the nipples and the rest of the fingers around the infant’s back, while the other does bag mask ventilation.

Compress the chest 1.5 inches in infants and 2 inches in children. Allow the chest to recoil between pushes and do at least 100 compressions per minute. "The key thing is to push hard and fast," said Dr. Gausche-Hill, professor of medicine at the University of California, Los Angeles. Do compressions for 2 minutes, then stop for no more than 10 seconds to check for a pulse. Mechanical devices for chest compressions have not been tested in children and should not be used in pediatric patients.

©2000 American Heart Association. Published by Elsevier Ireland Ltd. All rights reserved.

For a single rescuer, a ratio of compressions to ventilation of 30:2 is recommended, but for two rescuers in the ED the ratio is 15:2, with more emphasis on ventilation. Take care not to overventilate, she said.

"We overbag super amounts when we do resuscitation ventilation. You don’t need that much," she emphasized. "You want to squeeze the bag just until chest rise is initiated, and then begin the release phase." For children, this means about 10 breaths a minute. To avoid overbagging, a resuscitator can say "squeeze" as she squeezes the bag just until the chest starts to rise, then pause and say "release, release" to give time for the chest to recoil.

After beginning CPR, determine if the rhythm is shockable, and if so, use the defibrillator. Then do 2 minutes of CPR, give epinephrine, check the rhythm again, shock again. "It’s no more shock, shock, shock. You’re going to do 2 minutes of CPR in-between," she said.

The best option is a manual defibrillator with pediatric pads, she said, starting with 2 J and going up to 4 J if needed. But a dose even as high as 10 J is not harmful, according to Dr. Gausche-Hill. "If the patient is in persistent [ventricular fibrillation], I would strongly consider ramping it up, especially in the adolescent," she said. The new guidelines no longer require a pediatric attenuating device for an automated external defibrillator, and the standard automated external defibrillator can be used for any age (Circulation 2010;122:S876-908).

©2000 American Heart Association. Published by Elsevier Ireland Ltd. All rights reserved.

Cuffed endotracheal tubes (ETTs) are now preferred over the standard uncuffed tubes for intubation. "The bottom line is there’s no concern about cricoid pressure leading to necrosis. There’s no increased risk of subglottic stenosis by the use of these. That was really the main concern," she said. Cuffed ETTs are preferred in patients with poor lung compliance, a large glottic air leak, or high airway resistance. A randomized, controlled trial of 2,246 children found that those treated with a cuffed ETT did not have more postextubation stridor than those treated with an uncuffed ETT (4.4% vs. 4.7%) and were much less likely to need a tube exchange (2.1% vs. 30.8%) (Br. J. Anaesth. 2009;103:867-73). "Our PICU just says give it to everybody," she said. In pediatric patients, use a half-size smaller than their standard cuff size.

Cricoid pressure to present aspiration during intubation is not recommended in children, as it actually impedes the airway. Dr. Gausche-Hill prefers a jaw thrust or, in older kids, a little laryngeal manipulation.

In neonates, providing a lot of oxygen initially is harmful, leading to the creation of free radicals that may have an adverse neurologic effect (Circulation 2010;122:S909-19), but oxygen can be appropriate in older children, she said. "Bottom line is, give O₂ 100% and then back it down as quickly as you can," and aim to maintain an oxygen saturation of about 94%, said Dr. Gausche-Hill, who is also director of EMS and pediatric emergency medicine fellowships at Harbor-UCLA Medical Center in Torrance, Calif.

The guidelines now emphasize the use of capnography to monitor end-tidal CO₂ to confirm endotracheal tube placement and assess the adequacy of CPR. With capnography, "you may see [return of spontaneous circulation] before you can even detect a pulse," she said.

Foreign body aspiration "is your worst nightmare in the ED because you know if you can’t get it out, the patient’s going to die. And we do know that kids just do this all the time," she said. More than 90% of patients with this condition are younger than 5 years. "You always begin with basic life support maneuvers if they’re still conscious. For the infant, it’s back blows and chest thrusts until the object is expelled or they become unconscious." For the conscious older child, start with the Heimlich maneuver. In unconscious children, progress to chest compressions; if the foreign body is esophageal, chest compressions may remove it.

If the foreign body is lodged deeper in the airway, use direct laryngoscopy and remove the object with Magill forceps in the pediatric size. Some recent surveys showed that "18% of EDs in the country do not have pediatric Magills. Look in your airway kit. Make sure you have them," she stressed.

Last, family presence during resuscitation attempts should be promoted, she said. Almost a dozen studies have shown that parents want that option and should be included in decision making when possible, she noted.

Dr. Gausche-Hill reported having no significant financial relationships to disclose.

SAN FRANCISCO – Children in cardiopulmonary arrest require specialized resuscitation skills, and updated guidelines published late in 2010 contain some new recommendations, according to Dr. Marianne Gausche-Hill.

The recommended sequence for cardiopulmonary resuscitation (CPR) "has changed for all ages except for the newborn" to compressions, airway, breathing (CAB) – instead of airway, breathing, compressions (ABC) – when performed by a bystander. Emergency department (ED) providers usually will ventilate and do compressions simultaneously.

"If you’re doing bag mask [ventilation], the recommendation is just do your ventilations, and do compressions separately. If the patient has been intubated, you can do continued ventilations as you’re doing compressions," Dr. Gausche-Hill said at the annual meeting of the American College of Emergency Physicians.

In babies, if there is a single rescuer, chest compressions should be done using two fingers in the middle of the chest between the nipples (Circulation 2010;122:S862-75). With two rescuers, one can use the hand-encircling technique in which the thumbs are between the nipples and the rest of the fingers around the infant’s back, while the other does bag mask ventilation.

Compress the chest 1.5 inches in infants and 2 inches in children. Allow the chest to recoil between pushes and do at least 100 compressions per minute. "The key thing is to push hard and fast," said Dr. Gausche-Hill, professor of medicine at the University of California, Los Angeles. Do compressions for 2 minutes, then stop for no more than 10 seconds to check for a pulse. Mechanical devices for chest compressions have not been tested in children and should not be used in pediatric patients.

©2000 American Heart Association. Published by Elsevier Ireland Ltd. All rights reserved.

For a single rescuer, a ratio of compressions to ventilation of 30:2 is recommended, but for two rescuers in the ED the ratio is 15:2, with more emphasis on ventilation. Take care not to overventilate, she said.

"We overbag super amounts when we do resuscitation ventilation. You don’t need that much," she emphasized. "You want to squeeze the bag just until chest rise is initiated, and then begin the release phase." For children, this means about 10 breaths a minute. To avoid overbagging, a resuscitator can say "squeeze" as she squeezes the bag just until the chest starts to rise, then pause and say "release, release" to give time for the chest to recoil.

After beginning CPR, determine if the rhythm is shockable, and if so, use the defibrillator. Then do 2 minutes of CPR, give epinephrine, check the rhythm again, shock again. "It’s no more shock, shock, shock. You’re going to do 2 minutes of CPR in-between," she said.

The best option is a manual defibrillator with pediatric pads, she said, starting with 2 J and going up to 4 J if needed. But a dose even as high as 10 J is not harmful, according to Dr. Gausche-Hill. "If the patient is in persistent [ventricular fibrillation], I would strongly consider ramping it up, especially in the adolescent," she said. The new guidelines no longer require a pediatric attenuating device for an automated external defibrillator, and the standard automated external defibrillator can be used for any age (Circulation 2010;122:S876-908).

©2000 American Heart Association. Published by Elsevier Ireland Ltd. All rights reserved.

Cuffed endotracheal tubes (ETTs) are now preferred over the standard uncuffed tubes for intubation. "The bottom line is there’s no concern about cricoid pressure leading to necrosis. There’s no increased risk of subglottic stenosis by the use of these. That was really the main concern," she said. Cuffed ETTs are preferred in patients with poor lung compliance, a large glottic air leak, or high airway resistance. A randomized, controlled trial of 2,246 children found that those treated with a cuffed ETT did not have more postextubation stridor than those treated with an uncuffed ETT (4.4% vs. 4.7%) and were much less likely to need a tube exchange (2.1% vs. 30.8%) (Br. J. Anaesth. 2009;103:867-73). "Our PICU just says give it to everybody," she said. In pediatric patients, use a half-size smaller than their standard cuff size.

Cricoid pressure to present aspiration during intubation is not recommended in children, as it actually impedes the airway. Dr. Gausche-Hill prefers a jaw thrust or, in older kids, a little laryngeal manipulation.

In neonates, providing a lot of oxygen initially is harmful, leading to the creation of free radicals that may have an adverse neurologic effect (Circulation 2010;122:S909-19), but oxygen can be appropriate in older children, she said. "Bottom line is, give O₂ 100% and then back it down as quickly as you can," and aim to maintain an oxygen saturation of about 94%, said Dr. Gausche-Hill, who is also director of EMS and pediatric emergency medicine fellowships at Harbor-UCLA Medical Center in Torrance, Calif.

The guidelines now emphasize the use of capnography to monitor end-tidal CO₂ to confirm endotracheal tube placement and assess the adequacy of CPR. With capnography, "you may see [return of spontaneous circulation] before you can even detect a pulse," she said.

Foreign body aspiration "is your worst nightmare in the ED because you know if you can’t get it out, the patient’s going to die. And we do know that kids just do this all the time," she said. More than 90% of patients with this condition are younger than 5 years. "You always begin with basic life support maneuvers if they’re still conscious. For the infant, it’s back blows and chest thrusts until the object is expelled or they become unconscious." For the conscious older child, start with the Heimlich maneuver. In unconscious children, progress to chest compressions; if the foreign body is esophageal, chest compressions may remove it.

If the foreign body is lodged deeper in the airway, use direct laryngoscopy and remove the object with Magill forceps in the pediatric size. Some recent surveys showed that "18% of EDs in the country do not have pediatric Magills. Look in your airway kit. Make sure you have them," she stressed.

Last, family presence during resuscitation attempts should be promoted, she said. Almost a dozen studies have shown that parents want that option and should be included in decision making when possible, she noted.

Dr. Gausche-Hill reported having no significant financial relationships to disclose.