American Thoracic Society (ATS): International Conference 2012

SAN FRANCISCO – Perioperative infusions of sodium bicarbonate failed to reduce the risk of kidney injury in patients undergoing cardiac surgery in a multicenter randomized, double-blind, placebo-controlled trial in 427 patients.

The bicarbonate infusion increased the pH of both blood and urine in the 215-patient treatment group compared with 213 patients in a control group who got sodium chloride (saline) infusions, but 45% of the bicarbonate group and 44% of the placebo group developed kidney injury, a nonsignificant difference, Dr. Shay McGuinness and his associates reported at an international conference of the American Thoracic Society.

The study excluded patients with end-stage renal disease; patients having emergency cardiac surgery or planned off-pump cardiac surgery; and patients with known blood-borne infectious disease, chronic inflammatory disease, immunosuppression, or chronic moderate- to high-dose corticosteroid use.

"We cannot recommend the use of perioperative infusions of sodium bicarbonate to reduce cardiac surgery–associated kidney injury in these patients, and we do not believe further investigation of this therapy is justified," said Dr. McGuinness, an intensive care specialist at Auckland City Hospital, New Zealand.

The study defined kidney injury as an increase in creatinine of at least 25% from baseline or at least 0.5 mg/dL within the first 5 postoperative days.

The bicarbonate group and placebo group did not differ significantly in mean time on ventilation (21 and 25 hours, respectively), length of stay in the ICU (2 days each), length of stay in the hospital (13 days each), mortality in the ICU (3% and 2%, respectively), or 90-day mortality (4% and 2%).

The infusion strategy had started to catch on in New Zealand and Australia, but it’s unclear if anyone in the United States has pursued it, he said.

The study identified a high-risk group, got a plausible physiological treatment effect, and had good compliance and follow-up rates, but the clinical results were "absolutely negative," Dr. McGuinness said.

The investigators still are analyzing subgroups in the study, but "my gut feeling is that this is a completely negative study. There’s not even a hint of benefit. Walk away from it and find something else to study," he said.

To be in the study, patients having cardiac surgery at three centers in New Zealand and Australia had to have one or more risk factors for associated kidney injury. The rates of risk factors were similar between groups, including age over 70 (a mean of 58% of patients), preexisting renal impairment (14%), left ventricular ejection fraction below 35% (6%), valvular surgery with or without coronary artery surgery (72%), previous cardiac surgery involving sternotomy (16%), or insulin-dependent diabetes mellitus (6%). Measures of baseline renal function were similar between groups.

"What you see is standard cardiosurgical higher-risk patients" in the cohort, Dr. McGuinness said.

Infusions commenced at the start of anesthesia with a 1-mmol/mL solution, followed by 0.5 mmol/kg for 1 hour and 0.2 mmol/kg per hour for 23 hours.

Acid-base status and plasma levels of bicarbonate were similar between groups at baseline, but statistically and clinically significant differences emerged between groups at several time points after the infusion started.

Mean plasma bicarbonate levels in the bicarbonate and placebo groups were 25.72 mmol/L and 25.91 mmol/L at baseline, respectively, 27.03 and 24.35 mmol/L at 6 hours, 29.74 and 23.7 mmol/L at 24 hours, and 29.14 and 25.35 mmol/L at 48 hours.

Mean plasma pH levels in the bicarbonate and placebo groups were 7.40 and 7.41 at baseline, 7.40 and 7.37 at 6 hours, and 7.44 and 7.36 at 24 hours, respectively.

Mean urinary pH measures were 5.8 and 5.5 at baseline, 6.5 and 5.8 at 6 hours, and 7.3 and 5.2 at 24 hours, respectively.

Up to half of the 1 million patients who undergo open heart surgery each year will develop associated kidney injury with increased risk for further morbidity or death. The overall incidence of cardiac surgery–related kidney injury is approximately 5%-10% and probably is increasing, he said.

A previous pilot study by Dr. McGuinness and his associates of 100 patients at a single site had suggested that prophylactic perioperative infusions of sodium bicarbonate might reduce the risk of kidney injury. The investigators conducted the phase II trial before deciding whether or not to pursue a large phase III trial, which will not be happening based on these results.

The study was funded by Fisher & Paykel Healthcare and New Zealand medical organizations. Dr. McGuinness reported having no disclosures.

SAN FRANCISCO – Perioperative infusions of sodium bicarbonate failed to reduce the risk of kidney injury in patients undergoing cardiac surgery in a multicenter randomized, double-blind, placebo-controlled trial in 427 patients.

The bicarbonate infusion increased the pH of both blood and urine in the 215-patient treatment group compared with 213 patients in a control group who got sodium chloride (saline) infusions, but 45% of the bicarbonate group and 44% of the placebo group developed kidney injury, a nonsignificant difference, Dr. Shay McGuinness and his associates reported at an international conference of the American Thoracic Society.

The study excluded patients with end-stage renal disease; patients having emergency cardiac surgery or planned off-pump cardiac surgery; and patients with known blood-borne infectious disease, chronic inflammatory disease, immunosuppression, or chronic moderate- to high-dose corticosteroid use.

"We cannot recommend the use of perioperative infusions of sodium bicarbonate to reduce cardiac surgery–associated kidney injury in these patients, and we do not believe further investigation of this therapy is justified," said Dr. McGuinness, an intensive care specialist at Auckland City Hospital, New Zealand.

The study defined kidney injury as an increase in creatinine of at least 25% from baseline or at least 0.5 mg/dL within the first 5 postoperative days.

The bicarbonate group and placebo group did not differ significantly in mean time on ventilation (21 and 25 hours, respectively), length of stay in the ICU (2 days each), length of stay in the hospital (13 days each), mortality in the ICU (3% and 2%, respectively), or 90-day mortality (4% and 2%).

The infusion strategy had started to catch on in New Zealand and Australia, but it’s unclear if anyone in the United States has pursued it, he said.

The study identified a high-risk group, got a plausible physiological treatment effect, and had good compliance and follow-up rates, but the clinical results were "absolutely negative," Dr. McGuinness said.

The investigators still are analyzing subgroups in the study, but "my gut feeling is that this is a completely negative study. There’s not even a hint of benefit. Walk away from it and find something else to study," he said.

To be in the study, patients having cardiac surgery at three centers in New Zealand and Australia had to have one or more risk factors for associated kidney injury. The rates of risk factors were similar between groups, including age over 70 (a mean of 58% of patients), preexisting renal impairment (14%), left ventricular ejection fraction below 35% (6%), valvular surgery with or without coronary artery surgery (72%), previous cardiac surgery involving sternotomy (16%), or insulin-dependent diabetes mellitus (6%). Measures of baseline renal function were similar between groups.

"What you see is standard cardiosurgical higher-risk patients" in the cohort, Dr. McGuinness said.

Infusions commenced at the start of anesthesia with a 1-mmol/mL solution, followed by 0.5 mmol/kg for 1 hour and 0.2 mmol/kg per hour for 23 hours.

Acid-base status and plasma levels of bicarbonate were similar between groups at baseline, but statistically and clinically significant differences emerged between groups at several time points after the infusion started.

Mean plasma bicarbonate levels in the bicarbonate and placebo groups were 25.72 mmol/L and 25.91 mmol/L at baseline, respectively, 27.03 and 24.35 mmol/L at 6 hours, 29.74 and 23.7 mmol/L at 24 hours, and 29.14 and 25.35 mmol/L at 48 hours.

Mean plasma pH levels in the bicarbonate and placebo groups were 7.40 and 7.41 at baseline, 7.40 and 7.37 at 6 hours, and 7.44 and 7.36 at 24 hours, respectively.

Mean urinary pH measures were 5.8 and 5.5 at baseline, 6.5 and 5.8 at 6 hours, and 7.3 and 5.2 at 24 hours, respectively.

Up to half of the 1 million patients who undergo open heart surgery each year will develop associated kidney injury with increased risk for further morbidity or death. The overall incidence of cardiac surgery–related kidney injury is approximately 5%-10% and probably is increasing, he said.

A previous pilot study by Dr. McGuinness and his associates of 100 patients at a single site had suggested that prophylactic perioperative infusions of sodium bicarbonate might reduce the risk of kidney injury. The investigators conducted the phase II trial before deciding whether or not to pursue a large phase III trial, which will not be happening based on these results.

The study was funded by Fisher & Paykel Healthcare and New Zealand medical organizations. Dr. McGuinness reported having no disclosures.

SAN FRANCISCO – Perioperative infusions of sodium bicarbonate failed to reduce the risk of kidney injury in patients undergoing cardiac surgery in a multicenter randomized, double-blind, placebo-controlled trial in 427 patients.

The bicarbonate infusion increased the pH of both blood and urine in the 215-patient treatment group compared with 213 patients in a control group who got sodium chloride (saline) infusions, but 45% of the bicarbonate group and 44% of the placebo group developed kidney injury, a nonsignificant difference, Dr. Shay McGuinness and his associates reported at an international conference of the American Thoracic Society.

The study excluded patients with end-stage renal disease; patients having emergency cardiac surgery or planned off-pump cardiac surgery; and patients with known blood-borne infectious disease, chronic inflammatory disease, immunosuppression, or chronic moderate- to high-dose corticosteroid use.

"We cannot recommend the use of perioperative infusions of sodium bicarbonate to reduce cardiac surgery–associated kidney injury in these patients, and we do not believe further investigation of this therapy is justified," said Dr. McGuinness, an intensive care specialist at Auckland City Hospital, New Zealand.

The study defined kidney injury as an increase in creatinine of at least 25% from baseline or at least 0.5 mg/dL within the first 5 postoperative days.

The bicarbonate group and placebo group did not differ significantly in mean time on ventilation (21 and 25 hours, respectively), length of stay in the ICU (2 days each), length of stay in the hospital (13 days each), mortality in the ICU (3% and 2%, respectively), or 90-day mortality (4% and 2%).

The infusion strategy had started to catch on in New Zealand and Australia, but it’s unclear if anyone in the United States has pursued it, he said.

The study identified a high-risk group, got a plausible physiological treatment effect, and had good compliance and follow-up rates, but the clinical results were "absolutely negative," Dr. McGuinness said.

The investigators still are analyzing subgroups in the study, but "my gut feeling is that this is a completely negative study. There’s not even a hint of benefit. Walk away from it and find something else to study," he said.

To be in the study, patients having cardiac surgery at three centers in New Zealand and Australia had to have one or more risk factors for associated kidney injury. The rates of risk factors were similar between groups, including age over 70 (a mean of 58% of patients), preexisting renal impairment (14%), left ventricular ejection fraction below 35% (6%), valvular surgery with or without coronary artery surgery (72%), previous cardiac surgery involving sternotomy (16%), or insulin-dependent diabetes mellitus (6%). Measures of baseline renal function were similar between groups.

"What you see is standard cardiosurgical higher-risk patients" in the cohort, Dr. McGuinness said.

Infusions commenced at the start of anesthesia with a 1-mmol/mL solution, followed by 0.5 mmol/kg for 1 hour and 0.2 mmol/kg per hour for 23 hours.

Acid-base status and plasma levels of bicarbonate were similar between groups at baseline, but statistically and clinically significant differences emerged between groups at several time points after the infusion started.

Mean plasma bicarbonate levels in the bicarbonate and placebo groups were 25.72 mmol/L and 25.91 mmol/L at baseline, respectively, 27.03 and 24.35 mmol/L at 6 hours, 29.74 and 23.7 mmol/L at 24 hours, and 29.14 and 25.35 mmol/L at 48 hours.

Mean plasma pH levels in the bicarbonate and placebo groups were 7.40 and 7.41 at baseline, 7.40 and 7.37 at 6 hours, and 7.44 and 7.36 at 24 hours, respectively.

Mean urinary pH measures were 5.8 and 5.5 at baseline, 6.5 and 5.8 at 6 hours, and 7.3 and 5.2 at 24 hours, respectively.

Up to half of the 1 million patients who undergo open heart surgery each year will develop associated kidney injury with increased risk for further morbidity or death. The overall incidence of cardiac surgery–related kidney injury is approximately 5%-10% and probably is increasing, he said.

A previous pilot study by Dr. McGuinness and his associates of 100 patients at a single site had suggested that prophylactic perioperative infusions of sodium bicarbonate might reduce the risk of kidney injury. The investigators conducted the phase II trial before deciding whether or not to pursue a large phase III trial, which will not be happening based on these results.

The study was funded by Fisher & Paykel Healthcare and New Zealand medical organizations. Dr. McGuinness reported having no disclosures.

SAN FRANCISCO – Outpatient sleep apnea management by primary care physicians and nurses works as well as management by specialists in a sleep center and is less expensive, Australian researchers reported at the International Conference of the American Thoracic Society.

The team randomized 155 patients with symptomatic, moderate to severe obstructive sleep apnea (OSA) – all with baseline Epworth Sleepiness Scale (ESS) scores of at least 8 – to either standard management by sleep specialists with sleep-lab testing or outpatient management by their primary care doctor and a community-based nurse. Primary care management often involved home-based, autotitrating CPAP (continuous positive airway pressure), but providers in both arms were free to prescribe whatever treatment they thought best.

Obstructive sleep apnea had first been diagnosed by the primary care doctors using screening and ESS questionnaires, plus home oximetry testing with the ApneaLink device, manufactured by ResMed. They and the nurses had six hours of OSA training before the trial, plus training about common sleep disorders and their differential diagnoses. Nurses had an additional week of training at a sleep center.

After 6 months, patients managed by the primary care group had a mean ESS improvement of 4.9 points and a mean Functional Outcomes of Sleep Questionnaire (FOSQ) improvement of 2.3 points. The mean ESS improvement in the specialist group was 5.1, and the mean FOSQ improvement was 2.7. The differences were not statistically significant.

CPAP machines were being used a mean of 4.8 hours per day at 6 months in the primary care group and a mean of 5.4 hours per day in the specialist group. Again, the difference was not significant.

Outpatient OSA management saved more than $2,000 (AUS) per patient, as well.

"Our results show that using a simplified, ambulatory approach for the treatment of OSA in primary care is not clinically inferior to management of these patients in a specialist sleep center," said lead investigator Dr. Ching Li Chai-Coetzer of the Adelaide Institute for Sleep Health at the Repatriation General Hospital in Adelaide, Australia.

"We think in rural, remote areas and in the developing world, as obesity emerges and sleep apnea becomes more of a clinical issue, the traditional models of care are not going to be available to all patients. We think these results may have some important implications in these areas," said Dr. Nicholas Antic, also an investigator from the Adelaide Institute for Sleep Health.

Dr. Chai-Coetzer and Dr. Antic said they had no relevant financial conflicts. The equipment used in the study was donated by ResMed, Philips Respironics, and SomnoMed.

SAN FRANCISCO – Outpatient sleep apnea management by primary care physicians and nurses works as well as management by specialists in a sleep center and is less expensive, Australian researchers reported at the International Conference of the American Thoracic Society.

The team randomized 155 patients with symptomatic, moderate to severe obstructive sleep apnea (OSA) – all with baseline Epworth Sleepiness Scale (ESS) scores of at least 8 – to either standard management by sleep specialists with sleep-lab testing or outpatient management by their primary care doctor and a community-based nurse. Primary care management often involved home-based, autotitrating CPAP (continuous positive airway pressure), but providers in both arms were free to prescribe whatever treatment they thought best.

Obstructive sleep apnea had first been diagnosed by the primary care doctors using screening and ESS questionnaires, plus home oximetry testing with the ApneaLink device, manufactured by ResMed. They and the nurses had six hours of OSA training before the trial, plus training about common sleep disorders and their differential diagnoses. Nurses had an additional week of training at a sleep center.

After 6 months, patients managed by the primary care group had a mean ESS improvement of 4.9 points and a mean Functional Outcomes of Sleep Questionnaire (FOSQ) improvement of 2.3 points. The mean ESS improvement in the specialist group was 5.1, and the mean FOSQ improvement was 2.7. The differences were not statistically significant.

CPAP machines were being used a mean of 4.8 hours per day at 6 months in the primary care group and a mean of 5.4 hours per day in the specialist group. Again, the difference was not significant.

Outpatient OSA management saved more than $2,000 (AUS) per patient, as well.

"Our results show that using a simplified, ambulatory approach for the treatment of OSA in primary care is not clinically inferior to management of these patients in a specialist sleep center," said lead investigator Dr. Ching Li Chai-Coetzer of the Adelaide Institute for Sleep Health at the Repatriation General Hospital in Adelaide, Australia.

"We think in rural, remote areas and in the developing world, as obesity emerges and sleep apnea becomes more of a clinical issue, the traditional models of care are not going to be available to all patients. We think these results may have some important implications in these areas," said Dr. Nicholas Antic, also an investigator from the Adelaide Institute for Sleep Health.

Dr. Chai-Coetzer and Dr. Antic said they had no relevant financial conflicts. The equipment used in the study was donated by ResMed, Philips Respironics, and SomnoMed.

SAN FRANCISCO – Outpatient sleep apnea management by primary care physicians and nurses works as well as management by specialists in a sleep center and is less expensive, Australian researchers reported at the International Conference of the American Thoracic Society.

The team randomized 155 patients with symptomatic, moderate to severe obstructive sleep apnea (OSA) – all with baseline Epworth Sleepiness Scale (ESS) scores of at least 8 – to either standard management by sleep specialists with sleep-lab testing or outpatient management by their primary care doctor and a community-based nurse. Primary care management often involved home-based, autotitrating CPAP (continuous positive airway pressure), but providers in both arms were free to prescribe whatever treatment they thought best.

Obstructive sleep apnea had first been diagnosed by the primary care doctors using screening and ESS questionnaires, plus home oximetry testing with the ApneaLink device, manufactured by ResMed. They and the nurses had six hours of OSA training before the trial, plus training about common sleep disorders and their differential diagnoses. Nurses had an additional week of training at a sleep center.

After 6 months, patients managed by the primary care group had a mean ESS improvement of 4.9 points and a mean Functional Outcomes of Sleep Questionnaire (FOSQ) improvement of 2.3 points. The mean ESS improvement in the specialist group was 5.1, and the mean FOSQ improvement was 2.7. The differences were not statistically significant.

CPAP machines were being used a mean of 4.8 hours per day at 6 months in the primary care group and a mean of 5.4 hours per day in the specialist group. Again, the difference was not significant.

Outpatient OSA management saved more than $2,000 (AUS) per patient, as well.

"Our results show that using a simplified, ambulatory approach for the treatment of OSA in primary care is not clinically inferior to management of these patients in a specialist sleep center," said lead investigator Dr. Ching Li Chai-Coetzer of the Adelaide Institute for Sleep Health at the Repatriation General Hospital in Adelaide, Australia.

"We think in rural, remote areas and in the developing world, as obesity emerges and sleep apnea becomes more of a clinical issue, the traditional models of care are not going to be available to all patients. We think these results may have some important implications in these areas," said Dr. Nicholas Antic, also an investigator from the Adelaide Institute for Sleep Health.

Dr. Chai-Coetzer and Dr. Antic said they had no relevant financial conflicts. The equipment used in the study was donated by ResMed, Philips Respironics, and SomnoMed.

SAN FRANCISCO – More than a decade after the event, asthma, chronic obstructive pulmonary disease, and other respiratory symptoms are more common among lower Manhattan residents whose homes were covered with dust from the 9/11 attacks.

"All of these [respiratory] symptoms and diseases have elevated rates in this population," said Dr. Vinicius Antao of the Centers for Disease Control and Prevention’s Agency for Toxic Substances and Disease Registry, who led an investigation into the issue.

Photo Andrea Booher/ FEMA News Photo

"We found that after controlling for variables" such as age, sex, and smoking, "they are at least 50% more likely to report these [problems than are] those who didn’t have any damage done to their homes," he said.

People who cleaned up the dust with a wet mop, instead of a broom and dustpan, have fewer respiratory problems today. Wet mopping probably kept dust particles from resuspending.

"Now we know" that even brief catastrophic dust exposure can cause "symptoms for a long time," Dr. Antao said.

That finding "will inform public health decision making in terms of emergency preparedness. We need to evacuate a population in a circumstance like this," he said.

His team linked the self-reported health status of 6,463 people in the World Trade Center Health Registry, a longitudinal project that tracks outcomes for 9/11 survivors with the amount of damage they said the attacks did to their homes. The respondents all lived below Canal Street in lower Manhattan on Sept. 11, 2001. The research is ongoing, but the data analyzed were from 2003 to 2007.

Dr. Antao and his colleagues excluded people who helped with the cleanup at ground zero, and controlled for people caught up in the dust cloud that billowed through Manhattan after the towers came down. The dust was a mixture of fine powdered concrete products, metals, and minerals, including asbestos, among other things.

People who said there was a heavy dust layer in their home – so much dust, for instance, that they couldn’t read a newspaper that was covered with it – were more likely than were those with no dust in their homes to report shortness of breath (odds ratio, 1.74; 95% confidence interval, 1.45-2.10), wheezing (OR, 1.68; 95% CI, 1.36-2.08), chronic cough (OR, 1.58; 95% CI, 1.23-2.01), upper respiratory symptoms (OR, 1.37; 95% CI, 1.17-1.60), asthma (OR, 1.30; 95% CI, 1.01-1.70), and COPD (OR, 1.37; 95% CI, 1.02-1.84).

Their rates of asthma and COPD are "slightly higher" than rates in the general population, Dr. Antao said.

His team also found a significant, but less pervasive, association with respiratory symptoms in people who said the shock wave from the towers’ collapse blew out their windows or damaged their furniture.

Dr. Antao said he doesn’t think recall bias is at work, especially since years have passed since the 9/11 attacks, meaning that the shock of the event has worn off to some extent and is less likely to color survivors’ perceptions of its effects on their health. "We’ve looked at different aspects of that, and most of the results that we have indicate that these data are real," he said.

Dr. Antao said he has no relevant financial disclosures.

SAN FRANCISCO – More than a decade after the event, asthma, chronic obstructive pulmonary disease, and other respiratory symptoms are more common among lower Manhattan residents whose homes were covered with dust from the 9/11 attacks.

"All of these [respiratory] symptoms and diseases have elevated rates in this population," said Dr. Vinicius Antao of the Centers for Disease Control and Prevention’s Agency for Toxic Substances and Disease Registry, who led an investigation into the issue.

Photo Andrea Booher/ FEMA News Photo

"We found that after controlling for variables" such as age, sex, and smoking, "they are at least 50% more likely to report these [problems than are] those who didn’t have any damage done to their homes," he said.

People who cleaned up the dust with a wet mop, instead of a broom and dustpan, have fewer respiratory problems today. Wet mopping probably kept dust particles from resuspending.

"Now we know" that even brief catastrophic dust exposure can cause "symptoms for a long time," Dr. Antao said.

That finding "will inform public health decision making in terms of emergency preparedness. We need to evacuate a population in a circumstance like this," he said.

His team linked the self-reported health status of 6,463 people in the World Trade Center Health Registry, a longitudinal project that tracks outcomes for 9/11 survivors with the amount of damage they said the attacks did to their homes. The respondents all lived below Canal Street in lower Manhattan on Sept. 11, 2001. The research is ongoing, but the data analyzed were from 2003 to 2007.

Dr. Antao and his colleagues excluded people who helped with the cleanup at ground zero, and controlled for people caught up in the dust cloud that billowed through Manhattan after the towers came down. The dust was a mixture of fine powdered concrete products, metals, and minerals, including asbestos, among other things.

People who said there was a heavy dust layer in their home – so much dust, for instance, that they couldn’t read a newspaper that was covered with it – were more likely than were those with no dust in their homes to report shortness of breath (odds ratio, 1.74; 95% confidence interval, 1.45-2.10), wheezing (OR, 1.68; 95% CI, 1.36-2.08), chronic cough (OR, 1.58; 95% CI, 1.23-2.01), upper respiratory symptoms (OR, 1.37; 95% CI, 1.17-1.60), asthma (OR, 1.30; 95% CI, 1.01-1.70), and COPD (OR, 1.37; 95% CI, 1.02-1.84).

Their rates of asthma and COPD are "slightly higher" than rates in the general population, Dr. Antao said.

His team also found a significant, but less pervasive, association with respiratory symptoms in people who said the shock wave from the towers’ collapse blew out their windows or damaged their furniture.

Dr. Antao said he doesn’t think recall bias is at work, especially since years have passed since the 9/11 attacks, meaning that the shock of the event has worn off to some extent and is less likely to color survivors’ perceptions of its effects on their health. "We’ve looked at different aspects of that, and most of the results that we have indicate that these data are real," he said.

Dr. Antao said he has no relevant financial disclosures.

SAN FRANCISCO – More than a decade after the event, asthma, chronic obstructive pulmonary disease, and other respiratory symptoms are more common among lower Manhattan residents whose homes were covered with dust from the 9/11 attacks.

"All of these [respiratory] symptoms and diseases have elevated rates in this population," said Dr. Vinicius Antao of the Centers for Disease Control and Prevention’s Agency for Toxic Substances and Disease Registry, who led an investigation into the issue.

Photo Andrea Booher/ FEMA News Photo

"We found that after controlling for variables" such as age, sex, and smoking, "they are at least 50% more likely to report these [problems than are] those who didn’t have any damage done to their homes," he said.

People who cleaned up the dust with a wet mop, instead of a broom and dustpan, have fewer respiratory problems today. Wet mopping probably kept dust particles from resuspending.

"Now we know" that even brief catastrophic dust exposure can cause "symptoms for a long time," Dr. Antao said.

That finding "will inform public health decision making in terms of emergency preparedness. We need to evacuate a population in a circumstance like this," he said.

His team linked the self-reported health status of 6,463 people in the World Trade Center Health Registry, a longitudinal project that tracks outcomes for 9/11 survivors with the amount of damage they said the attacks did to their homes. The respondents all lived below Canal Street in lower Manhattan on Sept. 11, 2001. The research is ongoing, but the data analyzed were from 2003 to 2007.

Dr. Antao and his colleagues excluded people who helped with the cleanup at ground zero, and controlled for people caught up in the dust cloud that billowed through Manhattan after the towers came down. The dust was a mixture of fine powdered concrete products, metals, and minerals, including asbestos, among other things.

People who said there was a heavy dust layer in their home – so much dust, for instance, that they couldn’t read a newspaper that was covered with it – were more likely than were those with no dust in their homes to report shortness of breath (odds ratio, 1.74; 95% confidence interval, 1.45-2.10), wheezing (OR, 1.68; 95% CI, 1.36-2.08), chronic cough (OR, 1.58; 95% CI, 1.23-2.01), upper respiratory symptoms (OR, 1.37; 95% CI, 1.17-1.60), asthma (OR, 1.30; 95% CI, 1.01-1.70), and COPD (OR, 1.37; 95% CI, 1.02-1.84).

Their rates of asthma and COPD are "slightly higher" than rates in the general population, Dr. Antao said.

His team also found a significant, but less pervasive, association with respiratory symptoms in people who said the shock wave from the towers’ collapse blew out their windows or damaged their furniture.

Dr. Antao said he doesn’t think recall bias is at work, especially since years have passed since the 9/11 attacks, meaning that the shock of the event has worn off to some extent and is less likely to color survivors’ perceptions of its effects on their health. "We’ve looked at different aspects of that, and most of the results that we have indicate that these data are real," he said.

Dr. Antao said he has no relevant financial disclosures.

SAN FRANCISCO – Thromboprophylaxis with enoxaparin (Lovenox) did not reduce mortality among acutely ill, hospitalized medical patients in a trial funded by the maker of the low molecular weight heparin, Sanofi-Aventis.

Among 4,171 patients randomized to enoxaparin 40 mg subcutaneously for 10 days, plus or minus 4 days, all-cause 30-day mortality was 4.9%; among 4,136 randomized to placebo for the same amount of time, it was 4.8% (relative risk, 1.0; P = .83).

The major bleeding rate was below a half percent in both groups and not statistically different. Minor bleeding was seen in 1.8% in the enoxaparin group and 1.1% in the placebo group, a statistically significant difference, Dr. Samuel Goldhaber said at an international conference of the American Thoracic Society.

Commenting on the study, New England Journal of Medicine editor Dr. Jeffrey Drazen noted that, in the United States, the reflex has been to use prophylaxis on even low-risk patients for venous thromboembolism. "The reason we published these data was that maybe we should rethink this. Maybe we should be making decisions about who should be receiving pharmacologic prophylaxis based on factors other than the fact that they are in the hospital for an acute medical illness," he said.

Patients were hospitalized for acute decompensated heart failure, severe systemic infections, or active cancer. No mortality benefit was found for enoxaparin on subgroup analysis. Both groups wore knee-high elastic graduated compression stockings during the treatment phase of the trial (N. Engl. J. Med. 2011;365:2463-72).

The all-cause 1-90 day mortality curves for the two groups "were absolutely superimposable. We were quite surprised by the results," said Dr. Goldhaber, professor of medicine at Harvard Medical School and director of the venous thromboembolism research group at Brigham and Women’s Hospital, both in Boston.

They were surprised because enoxaparin has been proven to reduce venous thromboembolism in both surgical and medical patients, and to reduce the incidence of fatal pulmonary embolism and all-cause mortality in surgical patients.

There was a presumption it would save medical patients’ lives, too, although they have a lower pulmonary embolism rate. Current U.S. treatment guidelines recommend pharmacologic prophylaxis in both surgical and acutely-ill medical inpatients.

The study was conducted in China, India, Korea, Malaysia, Mexico, the Philippines, and Tunisia because, in those places, enoxaparin prophylaxis for medical patients is "still considered an open question," Dr. Goldhaber said.

About 88% of the subjects were Asian, 63% were men. Their average age was 65 years and average body mass index about 23 kg/m². There were no statistically significant baseline differences between the placebo and enoxaparin groups.

Perhaps enoxaparin didn’t cut mortality in the trial because "the natural history of deep vein thrombosis differs between medical and surgical patients." It’s been assumed that "the natural history would be the same. This assumption may be incorrect," Dr. Goldhaber said.

It’s also possible that the elastic stockings used in the trial were enough to prevent fatal pulmonary embolisms in the mostly-Asian subjects, a group known historically to have a lower pulmonary embolism risk than Westerners. Just one patient in each group died from a pulmonary embolism in the study; infections were the main cause of death.

At this point, Dr. Goldhaber still tends to prophylaxis even low-risk medical inpatients. "In our world, the quality measures are in place, but I’d be thinking to myself that prophylaxis is not going, in all likelihood, to save [their lives] from a pulmonary embolism because [they’re] probably not going to develop that problem," he said.

Dr. Goldhaber disclosed that he is a paid consultant for Sanofi-Aventis, Boehringer Ingelheim, Bristol Myers Squibb, Merck, and several other companies. Dr. Drazen reported having no disclosures.

SAN FRANCISCO – Thromboprophylaxis with enoxaparin (Lovenox) did not reduce mortality among acutely ill, hospitalized medical patients in a trial funded by the maker of the low molecular weight heparin, Sanofi-Aventis.

Among 4,171 patients randomized to enoxaparin 40 mg subcutaneously for 10 days, plus or minus 4 days, all-cause 30-day mortality was 4.9%; among 4,136 randomized to placebo for the same amount of time, it was 4.8% (relative risk, 1.0; P = .83).

The major bleeding rate was below a half percent in both groups and not statistically different. Minor bleeding was seen in 1.8% in the enoxaparin group and 1.1% in the placebo group, a statistically significant difference, Dr. Samuel Goldhaber said at an international conference of the American Thoracic Society.

Commenting on the study, New England Journal of Medicine editor Dr. Jeffrey Drazen noted that, in the United States, the reflex has been to use prophylaxis on even low-risk patients for venous thromboembolism. "The reason we published these data was that maybe we should rethink this. Maybe we should be making decisions about who should be receiving pharmacologic prophylaxis based on factors other than the fact that they are in the hospital for an acute medical illness," he said.

Patients were hospitalized for acute decompensated heart failure, severe systemic infections, or active cancer. No mortality benefit was found for enoxaparin on subgroup analysis. Both groups wore knee-high elastic graduated compression stockings during the treatment phase of the trial (N. Engl. J. Med. 2011;365:2463-72).

The all-cause 1-90 day mortality curves for the two groups "were absolutely superimposable. We were quite surprised by the results," said Dr. Goldhaber, professor of medicine at Harvard Medical School and director of the venous thromboembolism research group at Brigham and Women’s Hospital, both in Boston.

They were surprised because enoxaparin has been proven to reduce venous thromboembolism in both surgical and medical patients, and to reduce the incidence of fatal pulmonary embolism and all-cause mortality in surgical patients.

There was a presumption it would save medical patients’ lives, too, although they have a lower pulmonary embolism rate. Current U.S. treatment guidelines recommend pharmacologic prophylaxis in both surgical and acutely-ill medical inpatients.

The study was conducted in China, India, Korea, Malaysia, Mexico, the Philippines, and Tunisia because, in those places, enoxaparin prophylaxis for medical patients is "still considered an open question," Dr. Goldhaber said.

About 88% of the subjects were Asian, 63% were men. Their average age was 65 years and average body mass index about 23 kg/m². There were no statistically significant baseline differences between the placebo and enoxaparin groups.

Perhaps enoxaparin didn’t cut mortality in the trial because "the natural history of deep vein thrombosis differs between medical and surgical patients." It’s been assumed that "the natural history would be the same. This assumption may be incorrect," Dr. Goldhaber said.

It’s also possible that the elastic stockings used in the trial were enough to prevent fatal pulmonary embolisms in the mostly-Asian subjects, a group known historically to have a lower pulmonary embolism risk than Westerners. Just one patient in each group died from a pulmonary embolism in the study; infections were the main cause of death.

At this point, Dr. Goldhaber still tends to prophylaxis even low-risk medical inpatients. "In our world, the quality measures are in place, but I’d be thinking to myself that prophylaxis is not going, in all likelihood, to save [their lives] from a pulmonary embolism because [they’re] probably not going to develop that problem," he said.

Dr. Goldhaber disclosed that he is a paid consultant for Sanofi-Aventis, Boehringer Ingelheim, Bristol Myers Squibb, Merck, and several other companies. Dr. Drazen reported having no disclosures.

SAN FRANCISCO – Thromboprophylaxis with enoxaparin (Lovenox) did not reduce mortality among acutely ill, hospitalized medical patients in a trial funded by the maker of the low molecular weight heparin, Sanofi-Aventis.

Among 4,171 patients randomized to enoxaparin 40 mg subcutaneously for 10 days, plus or minus 4 days, all-cause 30-day mortality was 4.9%; among 4,136 randomized to placebo for the same amount of time, it was 4.8% (relative risk, 1.0; P = .83).

The major bleeding rate was below a half percent in both groups and not statistically different. Minor bleeding was seen in 1.8% in the enoxaparin group and 1.1% in the placebo group, a statistically significant difference, Dr. Samuel Goldhaber said at an international conference of the American Thoracic Society.

Commenting on the study, New England Journal of Medicine editor Dr. Jeffrey Drazen noted that, in the United States, the reflex has been to use prophylaxis on even low-risk patients for venous thromboembolism. "The reason we published these data was that maybe we should rethink this. Maybe we should be making decisions about who should be receiving pharmacologic prophylaxis based on factors other than the fact that they are in the hospital for an acute medical illness," he said.

Patients were hospitalized for acute decompensated heart failure, severe systemic infections, or active cancer. No mortality benefit was found for enoxaparin on subgroup analysis. Both groups wore knee-high elastic graduated compression stockings during the treatment phase of the trial (N. Engl. J. Med. 2011;365:2463-72).

The all-cause 1-90 day mortality curves for the two groups "were absolutely superimposable. We were quite surprised by the results," said Dr. Goldhaber, professor of medicine at Harvard Medical School and director of the venous thromboembolism research group at Brigham and Women’s Hospital, both in Boston.

They were surprised because enoxaparin has been proven to reduce venous thromboembolism in both surgical and medical patients, and to reduce the incidence of fatal pulmonary embolism and all-cause mortality in surgical patients.

There was a presumption it would save medical patients’ lives, too, although they have a lower pulmonary embolism rate. Current U.S. treatment guidelines recommend pharmacologic prophylaxis in both surgical and acutely-ill medical inpatients.

The study was conducted in China, India, Korea, Malaysia, Mexico, the Philippines, and Tunisia because, in those places, enoxaparin prophylaxis for medical patients is "still considered an open question," Dr. Goldhaber said.

About 88% of the subjects were Asian, 63% were men. Their average age was 65 years and average body mass index about 23 kg/m². There were no statistically significant baseline differences between the placebo and enoxaparin groups.

Perhaps enoxaparin didn’t cut mortality in the trial because "the natural history of deep vein thrombosis differs between medical and surgical patients." It’s been assumed that "the natural history would be the same. This assumption may be incorrect," Dr. Goldhaber said.

It’s also possible that the elastic stockings used in the trial were enough to prevent fatal pulmonary embolisms in the mostly-Asian subjects, a group known historically to have a lower pulmonary embolism risk than Westerners. Just one patient in each group died from a pulmonary embolism in the study; infections were the main cause of death.

At this point, Dr. Goldhaber still tends to prophylaxis even low-risk medical inpatients. "In our world, the quality measures are in place, but I’d be thinking to myself that prophylaxis is not going, in all likelihood, to save [their lives] from a pulmonary embolism because [they’re] probably not going to develop that problem," he said.

Dr. Goldhaber disclosed that he is a paid consultant for Sanofi-Aventis, Boehringer Ingelheim, Bristol Myers Squibb, Merck, and several other companies. Dr. Drazen reported having no disclosures.

SAN FRANCISCO – Overnight intensivist coverage reduces ICU mortality, but only in ICUs that don’t have robust intensivist coverage during the day, according to University of Pittsburgh researchers.

The team linked the outcomes of 65,752 ICU patients in the APACHE (Acute Physiologic and Chronic Health Evaluation) database from 2009-2010 to survey-assessed staffing practices at the 49 ICUs where they were treated.

In the 22 ICUs with low-intensity daytime staffing (meaning that intensivists weren’t routinely involved in patient care during the day and intensivist consults were only optional), having an intensivist present in the ICU at night – or at least immediately available to manage overnight ICU emergencies – was associated with a significant reduction in risk-adjusted, in-hospital mortality (odds ratio, 0.62; P = .04), the researchers said.

That wasn’t the case in the 27 ICUs with high-intensity daytime staffing, where intensivists had primary responsibility for patients during the day or intensivist consults were required for daytime admissions. Adding an overnight intensivist to expand that coverage to 24 hours did not significantly reduce risk-adjusted, in-hospital mortality (OR, 1.08; P = .78) (N. Engl. J. Med. 2012 May 21 [doi:10.1056/NEJMsa1201918]).

The critical care community – as well as hospitals, insurance providers, and legislators – have debated ICU staffing in the wake of studies showing that outcomes improve when intensivists manage ICU patients during the day (JAMA 2002;288:2151-62).

Among other questions on their minds was whether nighttime coverage would improve outcomes even more, senior author Dr. Jeremy Kahn, of the departments of critical care medicine and health policy at the University of Pittsburgh, said at the international conference of the American Thoracic Society.

"Our study indicates" that "ICUs with low-intensity daytime staffing, the most common staffing model in the United States, have better outcomes when intensivists are present at night. Nationally, two-thirds of ICUs have no intensivists at night, so expanding the role of intensivists in these ICUs could translate into improved health care quality," he said.

But ICUs with robust intensivist coverage during the day – and, frequently, resident coverage at night – do "not share the same benefit from nighttime intensivists. This shows that the movement to expand intensivist presence in these hospitals may be premature, especially since intensivists are in relatively short supply," Dr. Kahn said.

"Individual hospitals and ICUs will need to weigh the anticipated benefits of expanding intensivist nighttime coverage against those of other quality-improvement efforts in order to best serve their patients, staff, and community," he and his colleagues concluded in their report.

It’s unclear why overnight intensivists reduced mortality in ICUs where they did not have a robust daytime presence. Perhaps they ensured more timely resuscitation of unstable patients, quicker treatment initiations, and more efficient adjustments of complex therapies, the researchers said.

Dr. Kahn and Dr. Campbell reported no relevant disclosures.

SAN FRANCISCO – Overnight intensivist coverage reduces ICU mortality, but only in ICUs that don’t have robust intensivist coverage during the day, according to University of Pittsburgh researchers.

The team linked the outcomes of 65,752 ICU patients in the APACHE (Acute Physiologic and Chronic Health Evaluation) database from 2009-2010 to survey-assessed staffing practices at the 49 ICUs where they were treated.

In the 22 ICUs with low-intensity daytime staffing (meaning that intensivists weren’t routinely involved in patient care during the day and intensivist consults were only optional), having an intensivist present in the ICU at night – or at least immediately available to manage overnight ICU emergencies – was associated with a significant reduction in risk-adjusted, in-hospital mortality (odds ratio, 0.62; P = .04), the researchers said.

That wasn’t the case in the 27 ICUs with high-intensity daytime staffing, where intensivists had primary responsibility for patients during the day or intensivist consults were required for daytime admissions. Adding an overnight intensivist to expand that coverage to 24 hours did not significantly reduce risk-adjusted, in-hospital mortality (OR, 1.08; P = .78) (N. Engl. J. Med. 2012 May 21 [doi:10.1056/NEJMsa1201918]).

The critical care community – as well as hospitals, insurance providers, and legislators – have debated ICU staffing in the wake of studies showing that outcomes improve when intensivists manage ICU patients during the day (JAMA 2002;288:2151-62).

Among other questions on their minds was whether nighttime coverage would improve outcomes even more, senior author Dr. Jeremy Kahn, of the departments of critical care medicine and health policy at the University of Pittsburgh, said at the international conference of the American Thoracic Society.

"Our study indicates" that "ICUs with low-intensity daytime staffing, the most common staffing model in the United States, have better outcomes when intensivists are present at night. Nationally, two-thirds of ICUs have no intensivists at night, so expanding the role of intensivists in these ICUs could translate into improved health care quality," he said.

But ICUs with robust intensivist coverage during the day – and, frequently, resident coverage at night – do "not share the same benefit from nighttime intensivists. This shows that the movement to expand intensivist presence in these hospitals may be premature, especially since intensivists are in relatively short supply," Dr. Kahn said.

"Individual hospitals and ICUs will need to weigh the anticipated benefits of expanding intensivist nighttime coverage against those of other quality-improvement efforts in order to best serve their patients, staff, and community," he and his colleagues concluded in their report.

It’s unclear why overnight intensivists reduced mortality in ICUs where they did not have a robust daytime presence. Perhaps they ensured more timely resuscitation of unstable patients, quicker treatment initiations, and more efficient adjustments of complex therapies, the researchers said.

Dr. Kahn and Dr. Campbell reported no relevant disclosures.

SAN FRANCISCO – Overnight intensivist coverage reduces ICU mortality, but only in ICUs that don’t have robust intensivist coverage during the day, according to University of Pittsburgh researchers.

The team linked the outcomes of 65,752 ICU patients in the APACHE (Acute Physiologic and Chronic Health Evaluation) database from 2009-2010 to survey-assessed staffing practices at the 49 ICUs where they were treated.

In the 22 ICUs with low-intensity daytime staffing (meaning that intensivists weren’t routinely involved in patient care during the day and intensivist consults were only optional), having an intensivist present in the ICU at night – or at least immediately available to manage overnight ICU emergencies – was associated with a significant reduction in risk-adjusted, in-hospital mortality (odds ratio, 0.62; P = .04), the researchers said.

That wasn’t the case in the 27 ICUs with high-intensity daytime staffing, where intensivists had primary responsibility for patients during the day or intensivist consults were required for daytime admissions. Adding an overnight intensivist to expand that coverage to 24 hours did not significantly reduce risk-adjusted, in-hospital mortality (OR, 1.08; P = .78) (N. Engl. J. Med. 2012 May 21 [doi:10.1056/NEJMsa1201918]).

The critical care community – as well as hospitals, insurance providers, and legislators – have debated ICU staffing in the wake of studies showing that outcomes improve when intensivists manage ICU patients during the day (JAMA 2002;288:2151-62).

Among other questions on their minds was whether nighttime coverage would improve outcomes even more, senior author Dr. Jeremy Kahn, of the departments of critical care medicine and health policy at the University of Pittsburgh, said at the international conference of the American Thoracic Society.

"Our study indicates" that "ICUs with low-intensity daytime staffing, the most common staffing model in the United States, have better outcomes when intensivists are present at night. Nationally, two-thirds of ICUs have no intensivists at night, so expanding the role of intensivists in these ICUs could translate into improved health care quality," he said.

But ICUs with robust intensivist coverage during the day – and, frequently, resident coverage at night – do "not share the same benefit from nighttime intensivists. This shows that the movement to expand intensivist presence in these hospitals may be premature, especially since intensivists are in relatively short supply," Dr. Kahn said.

"Individual hospitals and ICUs will need to weigh the anticipated benefits of expanding intensivist nighttime coverage against those of other quality-improvement efforts in order to best serve their patients, staff, and community," he and his colleagues concluded in their report.

It’s unclear why overnight intensivists reduced mortality in ICUs where they did not have a robust daytime presence. Perhaps they ensured more timely resuscitation of unstable patients, quicker treatment initiations, and more efficient adjustments of complex therapies, the researchers said.

Dr. Kahn and Dr. Campbell reported no relevant disclosures.

SAN FRANCISCO – A phase III clinical trial ended early after preliminary results showed lower cure rates and higher death rates in patients with ventilator-associated pneumonia who were treated for 7 days with doripenem, compared with patients who received 10 days of imipenem.

With 274 patients randomized of a planned enrollment of 524 participants, the investigators conducted a modified intention-to-treat analysis of patients with qualifying bacterial organisms confirmed by bronchiolar lavage and culture. Clinical cure rates were 46% for doripenem and 57% for imipenem, and 28-day all-cause mortality rates were 22% for doripenem and 15% for imipenem, Dr. Marin H. Kollef and his associates reported in a late-breaker session at an international the conference of the American Thoracic Society.

The confidence intervals for both results crossed the threshold of no greater than a 15% difference between groups that would be required to say the doripenem regimen was noninferior to the imipenem regimen. Multiple overall and subgroup analyses showed trends favoring the safety and efficacy of the imipenem regimen, said Dr. Kollef, professor of medicine at Washington University and director of the medical ICU and of respiratory care services at Barnes-Jewish Hospital, both in St. Louis.

The difference in 28-day all-cause mortality did reach statistical significance in a subgroup of patients infected with P. aeruginosa, who were more likely to survive on imipenem therapy, he said.

Doripenem is a carbapenem antibiotic that is approved in the United States for the treatment of complicated urinary and abdominal infections caused by susceptible bacteria but is not approved for pneumonia. It is approved in many other countries for the treatment of nosocomial pneumonia, including ventilator-associated pneumonia (VAP).

The study, known as the DORINOS3008 study, used a higher dose of doripenem than is approved in other countries for pneumonia, the thinking being that a higher dosage might allow shorter duration of treatment. Patients randomized to doripenem received 1 g of doripenem in a 4-hour infusion every 8 hours for 7 days plus a 1-hour infusion of saline placebo every 8 hours for 10 days. The imipenem group received a 4-hour infusion of placebo every 8 hours for 7 days and a 1-hour infusion of imipenem every 8 hours for 10 days.

In the doripenem group, 44% of patients reached a creatinine clearance of at least 150 mL/min, compared with 71% of patients in the imipenem group.

The findings contradict results of a previous phase III study of VAP treated for 7-10 days at the discretion of the investigator. That study, known as DORI-10, reported noninferiority between a regimen of doripenem 500 mg in 4-hour infusions every 8 hours and treatment with imipenem 500 mg in 30-minute infusions every 6 hours or 1 g in 60-minute infusions every 8 hours. In that study, more than 90% of cured patients were treated for at least 8 days, and 35% of patients were treated for at least 10 days, Dr. Kollef noted (Crit. Care Med. 2008;36:1089-96).

In countries where doripenem is approved to treat ventilator-associated pneumonia, the usual duration of treatment is 7-14 days.

"I can’t give you the absolute explanation" for the differences in results from DORI-10 and DORINOS3008, but the findings suggest that physicians should consider treating VAP for longer than 7 days, Dr. Kollef said.

The current study included adult patients who had been hospitalized for at least 5 days, who were on mechanical ventilation, and who met clinical and radiographic criteria for pneumonia.

The study was funded by Johnson & Johnson, which markets doripenem. Dr. Kollef has been a speaker for Pfizer.

SAN FRANCISCO – A phase III clinical trial ended early after preliminary results showed lower cure rates and higher death rates in patients with ventilator-associated pneumonia who were treated for 7 days with doripenem, compared with patients who received 10 days of imipenem.

With 274 patients randomized of a planned enrollment of 524 participants, the investigators conducted a modified intention-to-treat analysis of patients with qualifying bacterial organisms confirmed by bronchiolar lavage and culture. Clinical cure rates were 46% for doripenem and 57% for imipenem, and 28-day all-cause mortality rates were 22% for doripenem and 15% for imipenem, Dr. Marin H. Kollef and his associates reported in a late-breaker session at an international the conference of the American Thoracic Society.

The confidence intervals for both results crossed the threshold of no greater than a 15% difference between groups that would be required to say the doripenem regimen was noninferior to the imipenem regimen. Multiple overall and subgroup analyses showed trends favoring the safety and efficacy of the imipenem regimen, said Dr. Kollef, professor of medicine at Washington University and director of the medical ICU and of respiratory care services at Barnes-Jewish Hospital, both in St. Louis.

The difference in 28-day all-cause mortality did reach statistical significance in a subgroup of patients infected with P. aeruginosa, who were more likely to survive on imipenem therapy, he said.

Doripenem is a carbapenem antibiotic that is approved in the United States for the treatment of complicated urinary and abdominal infections caused by susceptible bacteria but is not approved for pneumonia. It is approved in many other countries for the treatment of nosocomial pneumonia, including ventilator-associated pneumonia (VAP).

The study, known as the DORINOS3008 study, used a higher dose of doripenem than is approved in other countries for pneumonia, the thinking being that a higher dosage might allow shorter duration of treatment. Patients randomized to doripenem received 1 g of doripenem in a 4-hour infusion every 8 hours for 7 days plus a 1-hour infusion of saline placebo every 8 hours for 10 days. The imipenem group received a 4-hour infusion of placebo every 8 hours for 7 days and a 1-hour infusion of imipenem every 8 hours for 10 days.

In the doripenem group, 44% of patients reached a creatinine clearance of at least 150 mL/min, compared with 71% of patients in the imipenem group.

The findings contradict results of a previous phase III study of VAP treated for 7-10 days at the discretion of the investigator. That study, known as DORI-10, reported noninferiority between a regimen of doripenem 500 mg in 4-hour infusions every 8 hours and treatment with imipenem 500 mg in 30-minute infusions every 6 hours or 1 g in 60-minute infusions every 8 hours. In that study, more than 90% of cured patients were treated for at least 8 days, and 35% of patients were treated for at least 10 days, Dr. Kollef noted (Crit. Care Med. 2008;36:1089-96).

In countries where doripenem is approved to treat ventilator-associated pneumonia, the usual duration of treatment is 7-14 days.

"I can’t give you the absolute explanation" for the differences in results from DORI-10 and DORINOS3008, but the findings suggest that physicians should consider treating VAP for longer than 7 days, Dr. Kollef said.

The current study included adult patients who had been hospitalized for at least 5 days, who were on mechanical ventilation, and who met clinical and radiographic criteria for pneumonia.

The study was funded by Johnson & Johnson, which markets doripenem. Dr. Kollef has been a speaker for Pfizer.

SAN FRANCISCO – A phase III clinical trial ended early after preliminary results showed lower cure rates and higher death rates in patients with ventilator-associated pneumonia who were treated for 7 days with doripenem, compared with patients who received 10 days of imipenem.

With 274 patients randomized of a planned enrollment of 524 participants, the investigators conducted a modified intention-to-treat analysis of patients with qualifying bacterial organisms confirmed by bronchiolar lavage and culture. Clinical cure rates were 46% for doripenem and 57% for imipenem, and 28-day all-cause mortality rates were 22% for doripenem and 15% for imipenem, Dr. Marin H. Kollef and his associates reported in a late-breaker session at an international the conference of the American Thoracic Society.

The confidence intervals for both results crossed the threshold of no greater than a 15% difference between groups that would be required to say the doripenem regimen was noninferior to the imipenem regimen. Multiple overall and subgroup analyses showed trends favoring the safety and efficacy of the imipenem regimen, said Dr. Kollef, professor of medicine at Washington University and director of the medical ICU and of respiratory care services at Barnes-Jewish Hospital, both in St. Louis.

The difference in 28-day all-cause mortality did reach statistical significance in a subgroup of patients infected with P. aeruginosa, who were more likely to survive on imipenem therapy, he said.

Doripenem is a carbapenem antibiotic that is approved in the United States for the treatment of complicated urinary and abdominal infections caused by susceptible bacteria but is not approved for pneumonia. It is approved in many other countries for the treatment of nosocomial pneumonia, including ventilator-associated pneumonia (VAP).

The study, known as the DORINOS3008 study, used a higher dose of doripenem than is approved in other countries for pneumonia, the thinking being that a higher dosage might allow shorter duration of treatment. Patients randomized to doripenem received 1 g of doripenem in a 4-hour infusion every 8 hours for 7 days plus a 1-hour infusion of saline placebo every 8 hours for 10 days. The imipenem group received a 4-hour infusion of placebo every 8 hours for 7 days and a 1-hour infusion of imipenem every 8 hours for 10 days.

In the doripenem group, 44% of patients reached a creatinine clearance of at least 150 mL/min, compared with 71% of patients in the imipenem group.

The findings contradict results of a previous phase III study of VAP treated for 7-10 days at the discretion of the investigator. That study, known as DORI-10, reported noninferiority between a regimen of doripenem 500 mg in 4-hour infusions every 8 hours and treatment with imipenem 500 mg in 30-minute infusions every 6 hours or 1 g in 60-minute infusions every 8 hours. In that study, more than 90% of cured patients were treated for at least 8 days, and 35% of patients were treated for at least 10 days, Dr. Kollef noted (Crit. Care Med. 2008;36:1089-96).

In countries where doripenem is approved to treat ventilator-associated pneumonia, the usual duration of treatment is 7-14 days.

"I can’t give you the absolute explanation" for the differences in results from DORI-10 and DORINOS3008, but the findings suggest that physicians should consider treating VAP for longer than 7 days, Dr. Kollef said.

The current study included adult patients who had been hospitalized for at least 5 days, who were on mechanical ventilation, and who met clinical and radiographic criteria for pneumonia.

The study was funded by Johnson & Johnson, which markets doripenem. Dr. Kollef has been a speaker for Pfizer.

SAN FRANCISCO – Inhaled hypertonic saline did not reduce the number of pulmonary exacerbations in infants and children with cystic fibrosis in a randomized trial.

The trial pitted 7% hypertonic saline in 158 pediatric patients against 0.9% isotonic saline as a control in 163 patients. The solutions were nebulized twice daily for 48 weeks, with both groups getting albuterol or levalbuterol beforehand. The patients ranged in age from 4 to 60 months. Adherence was at least 75% in each group, judging from returned study drug ampoules, reported lead investigator Dr. Margaret Rosenfeld at an international conference of the American Thoracic Society.

In the hypertonic saline group, the mean pulmonary exacerbation rate was 2.3 events/person-year (95% confidence interval [CI], 2.0-2.5), and the mean number of total antibiotic treatment days for pulmonary exacerbations was 60 (95% CI, 49-70). In the control group, the mean pulmonary exacerbation rate was 2.3 events/person-year (95% CI, 2.1-2.6), and the mean total number of antibiotic treatment days was 52 (95% CI, 43-61).

No significant differences were seen in secondary end points, including height, weight, respiratory rate, oxygen saturation, cough, or respiratory symptom scores. Adverse event profiles were similar, with cough the most common adverse event in about 40% of each group (JAMA 2012 May 20 [doi:10.1001/jama.2012.5214]).

"There is great interest in the CF [cystic fibrosis] community about developing early intervention strategies to delay or prevent CF lung disease before the bronchiectasis becomes irreversible. From our current evidence, hypertonic saline does not fulfill that role. Based on its inability to reduce the rate of pulmonary exacerbations, we would not recommend that it be used in this age range," said Dr. Rosenfeld, a pediatric pulmonologist and associate professor of pediatrics at the University of Washington in Seattle.

The finding was a surprise because hypertonic saline is known to prevent exacerbations in older children and adults, perhaps by helping the lungs cough out bacteria. There has been hope it would also help very young children, and its use in that population has increased substantially in recent years, Dr. Rosenfeld noted (N. Engl. J. Med. 2006;354:229-40).

"We’ve been scratching our heads about" why that hope didn’t pan out in the trial. "We have a number of hypotheses. The first one is that pulmonary exacerbations may be really different beasts in infants and young children. [Perhaps] they are mostly triggered by viral respiratory infections. Hypertonic saline can’t prevent people from getting respiratory viruses," she said at the conference.

Exacerbations might have been too blunt a primary outcome measure, according to an editorial that accompanied the published study in JAMA.

Very young children with CF have not yet developed the outright lung damage that makes older patients particularly susceptible to exacerbations. Perhaps more subtle markers of early disease onset and progression were needed in the trial, wrote Dr. Elliott Dasenbrook, associate director of the Adult Cystic Fibrosis Program at Case Western Reserve University, Cleveland, and Dr. Michael Konstan, director of the school’s Cystic Fibrosis Center and chairman of its pediatrics department.

"Although the results of the study suggest that inhaled hypertonic saline should not be used routinely in young children, the final verdict on its use for infants and young children has not been rendered. It would be disheartening if a viable therapeutic option was discarded because of negative study results when more sensitive end points might have detected benefit from the intervention. Testing therapeutic agents in infants and young children may require different end points capable of assessing onset and progression of disease," they wrote (JAMA 2012 May 20 [doi: 10.1001/jama.2012.5853]).

There was one "tantalizing" hint in the trial that hypertonic saline may delay structural damage, Dr. Rosenfeld said. Among the 22 children aged 4-16 months in the hypertonic saline group who had pulmonary function tests, forced expiratory volume in 0.5 seconds (FEV_0.5) was a mean of 38 mL greater (95% CI, 1-76) than among the 23 children tested in the control group, the only significant pulmonary function difference.

Perhaps that could be a marker in future trials, but "statistically significant difference does not necessarily imply clinical significance," Dr. Dasenbrook and Dr. Konstan noted. "Even though the results of infant pulmonary function testing appear encouraging, ... these exploratory end points should be viewed as hypothesis generating, and research exploring the clinical effects of these differences is needed."

That research is likely to happen. "We would like to study [hypertonic saline] further and see if we get a signal if we choose more physiologic end points," Dr. Rosenfeld said.

Dr. Rosenfeld disclosed that she is an adviser to Genentech and Vertex Pharmaceuticals, and receives research grants from Vertex. Dr. Dasenbrook is a consultant for Savara and Gilead. Dr. Konstan is an adviser to Aradigm and a consultant for Boehringer Ingelheim, Genentech, Novartis, PARI Respiratory Equipment, Vertex, and several other companies. He receives grants or has grants pending from several companies, and receives speaker’s fees from Genentech and Novartis.

SAN FRANCISCO – Inhaled hypertonic saline did not reduce the number of pulmonary exacerbations in infants and children with cystic fibrosis in a randomized trial.

The trial pitted 7% hypertonic saline in 158 pediatric patients against 0.9% isotonic saline as a control in 163 patients. The solutions were nebulized twice daily for 48 weeks, with both groups getting albuterol or levalbuterol beforehand. The patients ranged in age from 4 to 60 months. Adherence was at least 75% in each group, judging from returned study drug ampoules, reported lead investigator Dr. Margaret Rosenfeld at an international conference of the American Thoracic Society.

In the hypertonic saline group, the mean pulmonary exacerbation rate was 2.3 events/person-year (95% confidence interval [CI], 2.0-2.5), and the mean number of total antibiotic treatment days for pulmonary exacerbations was 60 (95% CI, 49-70). In the control group, the mean pulmonary exacerbation rate was 2.3 events/person-year (95% CI, 2.1-2.6), and the mean total number of antibiotic treatment days was 52 (95% CI, 43-61).

No significant differences were seen in secondary end points, including height, weight, respiratory rate, oxygen saturation, cough, or respiratory symptom scores. Adverse event profiles were similar, with cough the most common adverse event in about 40% of each group (JAMA 2012 May 20 [doi:10.1001/jama.2012.5214]).

"There is great interest in the CF [cystic fibrosis] community about developing early intervention strategies to delay or prevent CF lung disease before the bronchiectasis becomes irreversible. From our current evidence, hypertonic saline does not fulfill that role. Based on its inability to reduce the rate of pulmonary exacerbations, we would not recommend that it be used in this age range," said Dr. Rosenfeld, a pediatric pulmonologist and associate professor of pediatrics at the University of Washington in Seattle.

The finding was a surprise because hypertonic saline is known to prevent exacerbations in older children and adults, perhaps by helping the lungs cough out bacteria. There has been hope it would also help very young children, and its use in that population has increased substantially in recent years, Dr. Rosenfeld noted (N. Engl. J. Med. 2006;354:229-40).

"We’ve been scratching our heads about" why that hope didn’t pan out in the trial. "We have a number of hypotheses. The first one is that pulmonary exacerbations may be really different beasts in infants and young children. [Perhaps] they are mostly triggered by viral respiratory infections. Hypertonic saline can’t prevent people from getting respiratory viruses," she said at the conference.

Exacerbations might have been too blunt a primary outcome measure, according to an editorial that accompanied the published study in JAMA.

Very young children with CF have not yet developed the outright lung damage that makes older patients particularly susceptible to exacerbations. Perhaps more subtle markers of early disease onset and progression were needed in the trial, wrote Dr. Elliott Dasenbrook, associate director of the Adult Cystic Fibrosis Program at Case Western Reserve University, Cleveland, and Dr. Michael Konstan, director of the school’s Cystic Fibrosis Center and chairman of its pediatrics department.

"Although the results of the study suggest that inhaled hypertonic saline should not be used routinely in young children, the final verdict on its use for infants and young children has not been rendered. It would be disheartening if a viable therapeutic option was discarded because of negative study results when more sensitive end points might have detected benefit from the intervention. Testing therapeutic agents in infants and young children may require different end points capable of assessing onset and progression of disease," they wrote (JAMA 2012 May 20 [doi: 10.1001/jama.2012.5853]).

There was one "tantalizing" hint in the trial that hypertonic saline may delay structural damage, Dr. Rosenfeld said. Among the 22 children aged 4-16 months in the hypertonic saline group who had pulmonary function tests, forced expiratory volume in 0.5 seconds (FEV_0.5) was a mean of 38 mL greater (95% CI, 1-76) than among the 23 children tested in the control group, the only significant pulmonary function difference.

Perhaps that could be a marker in future trials, but "statistically significant difference does not necessarily imply clinical significance," Dr. Dasenbrook and Dr. Konstan noted. "Even though the results of infant pulmonary function testing appear encouraging, ... these exploratory end points should be viewed as hypothesis generating, and research exploring the clinical effects of these differences is needed."

That research is likely to happen. "We would like to study [hypertonic saline] further and see if we get a signal if we choose more physiologic end points," Dr. Rosenfeld said.

Dr. Rosenfeld disclosed that she is an adviser to Genentech and Vertex Pharmaceuticals, and receives research grants from Vertex. Dr. Dasenbrook is a consultant for Savara and Gilead. Dr. Konstan is an adviser to Aradigm and a consultant for Boehringer Ingelheim, Genentech, Novartis, PARI Respiratory Equipment, Vertex, and several other companies. He receives grants or has grants pending from several companies, and receives speaker’s fees from Genentech and Novartis.

SAN FRANCISCO – Inhaled hypertonic saline did not reduce the number of pulmonary exacerbations in infants and children with cystic fibrosis in a randomized trial.

The trial pitted 7% hypertonic saline in 158 pediatric patients against 0.9% isotonic saline as a control in 163 patients. The solutions were nebulized twice daily for 48 weeks, with both groups getting albuterol or levalbuterol beforehand. The patients ranged in age from 4 to 60 months. Adherence was at least 75% in each group, judging from returned study drug ampoules, reported lead investigator Dr. Margaret Rosenfeld at an international conference of the American Thoracic Society.

In the hypertonic saline group, the mean pulmonary exacerbation rate was 2.3 events/person-year (95% confidence interval [CI], 2.0-2.5), and the mean number of total antibiotic treatment days for pulmonary exacerbations was 60 (95% CI, 49-70). In the control group, the mean pulmonary exacerbation rate was 2.3 events/person-year (95% CI, 2.1-2.6), and the mean total number of antibiotic treatment days was 52 (95% CI, 43-61).

No significant differences were seen in secondary end points, including height, weight, respiratory rate, oxygen saturation, cough, or respiratory symptom scores. Adverse event profiles were similar, with cough the most common adverse event in about 40% of each group (JAMA 2012 May 20 [doi:10.1001/jama.2012.5214]).

"There is great interest in the CF [cystic fibrosis] community about developing early intervention strategies to delay or prevent CF lung disease before the bronchiectasis becomes irreversible. From our current evidence, hypertonic saline does not fulfill that role. Based on its inability to reduce the rate of pulmonary exacerbations, we would not recommend that it be used in this age range," said Dr. Rosenfeld, a pediatric pulmonologist and associate professor of pediatrics at the University of Washington in Seattle.

The finding was a surprise because hypertonic saline is known to prevent exacerbations in older children and adults, perhaps by helping the lungs cough out bacteria. There has been hope it would also help very young children, and its use in that population has increased substantially in recent years, Dr. Rosenfeld noted (N. Engl. J. Med. 2006;354:229-40).

"We’ve been scratching our heads about" why that hope didn’t pan out in the trial. "We have a number of hypotheses. The first one is that pulmonary exacerbations may be really different beasts in infants and young children. [Perhaps] they are mostly triggered by viral respiratory infections. Hypertonic saline can’t prevent people from getting respiratory viruses," she said at the conference.

Exacerbations might have been too blunt a primary outcome measure, according to an editorial that accompanied the published study in JAMA.

Very young children with CF have not yet developed the outright lung damage that makes older patients particularly susceptible to exacerbations. Perhaps more subtle markers of early disease onset and progression were needed in the trial, wrote Dr. Elliott Dasenbrook, associate director of the Adult Cystic Fibrosis Program at Case Western Reserve University, Cleveland, and Dr. Michael Konstan, director of the school’s Cystic Fibrosis Center and chairman of its pediatrics department.

"Although the results of the study suggest that inhaled hypertonic saline should not be used routinely in young children, the final verdict on its use for infants and young children has not been rendered. It would be disheartening if a viable therapeutic option was discarded because of negative study results when more sensitive end points might have detected benefit from the intervention. Testing therapeutic agents in infants and young children may require different end points capable of assessing onset and progression of disease," they wrote (JAMA 2012 May 20 [doi: 10.1001/jama.2012.5853]).

There was one "tantalizing" hint in the trial that hypertonic saline may delay structural damage, Dr. Rosenfeld said. Among the 22 children aged 4-16 months in the hypertonic saline group who had pulmonary function tests, forced expiratory volume in 0.5 seconds (FEV_0.5) was a mean of 38 mL greater (95% CI, 1-76) than among the 23 children tested in the control group, the only significant pulmonary function difference.

Perhaps that could be a marker in future trials, but "statistically significant difference does not necessarily imply clinical significance," Dr. Dasenbrook and Dr. Konstan noted. "Even though the results of infant pulmonary function testing appear encouraging, ... these exploratory end points should be viewed as hypothesis generating, and research exploring the clinical effects of these differences is needed."

That research is likely to happen. "We would like to study [hypertonic saline] further and see if we get a signal if we choose more physiologic end points," Dr. Rosenfeld said.

Dr. Rosenfeld disclosed that she is an adviser to Genentech and Vertex Pharmaceuticals, and receives research grants from Vertex. Dr. Dasenbrook is a consultant for Savara and Gilead. Dr. Konstan is an adviser to Aradigm and a consultant for Boehringer Ingelheim, Genentech, Novartis, PARI Respiratory Equipment, Vertex, and several other companies. He receives grants or has grants pending from several companies, and receives speaker’s fees from Genentech and Novartis.

SAN FRANCISCO – Treating a new diagnosis of severe sepsis or septic shock with a combination of moxifloxacin and meropenem did not decrease the risk of sepsis-related organ dysfunction, compared with meropenem monotherapy, in a randomized, open-label trial.

On the contrary, there were statistical hints suggesting that the monotherapy regimen may be safer than the dual-drug strategy, Dr. Tobias Welte and his associates reported at an international conference of the American Thoracic Society.

Mean daily scores on the SOFA (Sequential Organ Failure Assessment) for 551 patients with evaluable data did not differ significantly between groups (a score of 8 in both) during treatment for 7-14 days or until discharge from the ICU or death, said Dr. Welte of Hannover (Germany) Medical School. Subscores on the SOFA for cardiovascular, respiratory, coagulation, renal, or hepatic failure also were similar between groups.

Among secondary outcomes, mortality rates at 28 days were 24% with the combination therapy and 22% with monotherapy. Mortality rates at 90 days were 35% with combination therapy and 32% with monotherapy. Those differences between groups were not significant, he said.

The combination therapy group had a significantly higher rate of treatment-related adverse events (9%), compared with the monotherapy group (4%).

The study was published online on May 21 in JAMA (doi:10.1001/jama.2012.5833).

The investigators had expected that the combination regimen would improve clinical outcomes. Use of empirical therapy with combined antibiotics has been controversial and is more common in the United States than in Europe.

Germany has a relatively low rate of antibiotic-resistant organisms, and the study had a relatively low rate of drug resistance. In patients with a first episode of severe sepsis or septic shock without risk factors for resistance to multiple antibiotics, monotherapy with a drug like meropenem is a good choice, Dr. Welte said.

"What we need for the future is a better characterization of patients who are at risk for multiresistant organisms," he said. "If you do it like the Americans do it, every patient is at risk for multiresistancy."He said he believes that with more precise risk stratification, more than half of U.S. patients with severe sepsis or septic shock might be candidates for monotherapy. Both groups averaged 8 days of treatment, showing that "8 days of treatment are enough even in patients with severe sepsis or septic shock," Dr. Welte said. One of the reasons for increased rates of multidrug-resistant organisms in the United States is overuse of antibiotics, he added. If treatment for severe sepsis were limited to one drug for only 7-8 days in areas with low rates of resistance, drug use in these cases could be reduced twofold, he suggested.

The MaxSep (Treatment of Severe Sepsis and Septic Shock) study included patients from 44 ICUs in Germany between October 2007 and March 2010. Intravenous infusions delivered 1-g meropenem every 8 hours plus moxifloxacin 400 mg every 24 hours, or meropenem alone. Survivors were followed for 90 days.

Baseline characteristics were similar between groups. After treatment, the results were similar between groups in ICU or hospital length of stay, median intervention-free days, and rate of secondary infection.

Notably, half of the infections were community acquired, which adds to the generalizability of the findings, Dr. Welte said.

In previous retrospective cohort studies, survival in severe sepsis significantly improved with a combination of beta-lactam antibiotics plus aminoglycosides, fluoroquinolones, macrolides, or clindamycin, compared with monotherapy (Crit. Care Med. 2010;38:1651-64).

Dr. Frank M. Brunkhorst of Friedrich Schiller University Jena (Germany) was the lead investigator in the study.

The study was funded by German government ministries and foundations. AstraZeneca and Bayer HealthCare provided the drugs for the study. Dr. Welte reported financial relationships with AstraZeneca, Bayer HealthCare, Astellas, GlaxoSmithKline, Novartis, and Pfizer. Some of his associates in the study reported relationships with these and other pharmaceutical companies.

SAN FRANCISCO – Treating a new diagnosis of severe sepsis or septic shock with a combination of moxifloxacin and meropenem did not decrease the risk of sepsis-related organ dysfunction, compared with meropenem monotherapy, in a randomized, open-label trial.

On the contrary, there were statistical hints suggesting that the monotherapy regimen may be safer than the dual-drug strategy, Dr. Tobias Welte and his associates reported at an international conference of the American Thoracic Society.

Mean daily scores on the SOFA (Sequential Organ Failure Assessment) for 551 patients with evaluable data did not differ significantly between groups (a score of 8 in both) during treatment for 7-14 days or until discharge from the ICU or death, said Dr. Welte of Hannover (Germany) Medical School. Subscores on the SOFA for cardiovascular, respiratory, coagulation, renal, or hepatic failure also were similar between groups.

Among secondary outcomes, mortality rates at 28 days were 24% with the combination therapy and 22% with monotherapy. Mortality rates at 90 days were 35% with combination therapy and 32% with monotherapy. Those differences between groups were not significant, he said.

The combination therapy group had a significantly higher rate of treatment-related adverse events (9%), compared with the monotherapy group (4%).

The study was published online on May 21 in JAMA (doi:10.1001/jama.2012.5833).

The investigators had expected that the combination regimen would improve clinical outcomes. Use of empirical therapy with combined antibiotics has been controversial and is more common in the United States than in Europe.

Germany has a relatively low rate of antibiotic-resistant organisms, and the study had a relatively low rate of drug resistance. In patients with a first episode of severe sepsis or septic shock without risk factors for resistance to multiple antibiotics, monotherapy with a drug like meropenem is a good choice, Dr. Welte said.

"What we need for the future is a better characterization of patients who are at risk for multiresistant organisms," he said. "If you do it like the Americans do it, every patient is at risk for multiresistancy."He said he believes that with more precise risk stratification, more than half of U.S. patients with severe sepsis or septic shock might be candidates for monotherapy. Both groups averaged 8 days of treatment, showing that "8 days of treatment are enough even in patients with severe sepsis or septic shock," Dr. Welte said. One of the reasons for increased rates of multidrug-resistant organisms in the United States is overuse of antibiotics, he added. If treatment for severe sepsis were limited to one drug for only 7-8 days in areas with low rates of resistance, drug use in these cases could be reduced twofold, he suggested.

The MaxSep (Treatment of Severe Sepsis and Septic Shock) study included patients from 44 ICUs in Germany between October 2007 and March 2010. Intravenous infusions delivered 1-g meropenem every 8 hours plus moxifloxacin 400 mg every 24 hours, or meropenem alone. Survivors were followed for 90 days.

Baseline characteristics were similar between groups. After treatment, the results were similar between groups in ICU or hospital length of stay, median intervention-free days, and rate of secondary infection.

Notably, half of the infections were community acquired, which adds to the generalizability of the findings, Dr. Welte said.

In previous retrospective cohort studies, survival in severe sepsis significantly improved with a combination of beta-lactam antibiotics plus aminoglycosides, fluoroquinolones, macrolides, or clindamycin, compared with monotherapy (Crit. Care Med. 2010;38:1651-64).

Dr. Frank M. Brunkhorst of Friedrich Schiller University Jena (Germany) was the lead investigator in the study.

The study was funded by German government ministries and foundations. AstraZeneca and Bayer HealthCare provided the drugs for the study. Dr. Welte reported financial relationships with AstraZeneca, Bayer HealthCare, Astellas, GlaxoSmithKline, Novartis, and Pfizer. Some of his associates in the study reported relationships with these and other pharmaceutical companies.

SAN FRANCISCO – Treating a new diagnosis of severe sepsis or septic shock with a combination of moxifloxacin and meropenem did not decrease the risk of sepsis-related organ dysfunction, compared with meropenem monotherapy, in a randomized, open-label trial.

On the contrary, there were statistical hints suggesting that the monotherapy regimen may be safer than the dual-drug strategy, Dr. Tobias Welte and his associates reported at an international conference of the American Thoracic Society.

Mean daily scores on the SOFA (Sequential Organ Failure Assessment) for 551 patients with evaluable data did not differ significantly between groups (a score of 8 in both) during treatment for 7-14 days or until discharge from the ICU or death, said Dr. Welte of Hannover (Germany) Medical School. Subscores on the SOFA for cardiovascular, respiratory, coagulation, renal, or hepatic failure also were similar between groups.

Among secondary outcomes, mortality rates at 28 days were 24% with the combination therapy and 22% with monotherapy. Mortality rates at 90 days were 35% with combination therapy and 32% with monotherapy. Those differences between groups were not significant, he said.

The combination therapy group had a significantly higher rate of treatment-related adverse events (9%), compared with the monotherapy group (4%).

The study was published online on May 21 in JAMA (doi:10.1001/jama.2012.5833).

The investigators had expected that the combination regimen would improve clinical outcomes. Use of empirical therapy with combined antibiotics has been controversial and is more common in the United States than in Europe.

Germany has a relatively low rate of antibiotic-resistant organisms, and the study had a relatively low rate of drug resistance. In patients with a first episode of severe sepsis or septic shock without risk factors for resistance to multiple antibiotics, monotherapy with a drug like meropenem is a good choice, Dr. Welte said.

"What we need for the future is a better characterization of patients who are at risk for multiresistant organisms," he said. "If you do it like the Americans do it, every patient is at risk for multiresistancy."He said he believes that with more precise risk stratification, more than half of U.S. patients with severe sepsis or septic shock might be candidates for monotherapy. Both groups averaged 8 days of treatment, showing that "8 days of treatment are enough even in patients with severe sepsis or septic shock," Dr. Welte said. One of the reasons for increased rates of multidrug-resistant organisms in the United States is overuse of antibiotics, he added. If treatment for severe sepsis were limited to one drug for only 7-8 days in areas with low rates of resistance, drug use in these cases could be reduced twofold, he suggested.

The MaxSep (Treatment of Severe Sepsis and Septic Shock) study included patients from 44 ICUs in Germany between October 2007 and March 2010. Intravenous infusions delivered 1-g meropenem every 8 hours plus moxifloxacin 400 mg every 24 hours, or meropenem alone. Survivors were followed for 90 days.

Baseline characteristics were similar between groups. After treatment, the results were similar between groups in ICU or hospital length of stay, median intervention-free days, and rate of secondary infection.

Notably, half of the infections were community acquired, which adds to the generalizability of the findings, Dr. Welte said.

In previous retrospective cohort studies, survival in severe sepsis significantly improved with a combination of beta-lactam antibiotics plus aminoglycosides, fluoroquinolones, macrolides, or clindamycin, compared with monotherapy (Crit. Care Med. 2010;38:1651-64).

Dr. Frank M. Brunkhorst of Friedrich Schiller University Jena (Germany) was the lead investigator in the study.

The study was funded by German government ministries and foundations. AstraZeneca and Bayer HealthCare provided the drugs for the study. Dr. Welte reported financial relationships with AstraZeneca, Bayer HealthCare, Astellas, GlaxoSmithKline, Novartis, and Pfizer. Some of his associates in the study reported relationships with these and other pharmaceutical companies.

SAN FRANCISCO – A proposed new definition of acute respiratory distress syndrome describes categories based on mild, moderate, or severe hypoxemia that correlate increasing severity with significantly increased mortality or increased time on mechanical ventilation among survivors.

The draft definition, created under consensus process by an international panel of experts, was refined by empirical testing in a meta-analysis of data on 4,457 patients in two large data sets from seven centers. The risk of mortality from acute respiratory distress syndrome (ARDS) was 27% with mild disease, 32% with moderate ARDS, and 45% with severe ARDS, Dr. Niall D. Ferguson and Dr. Gordon D. Rubenfeld reported at an international conference of the American Thoracic Society.

Sherry Boschert/IMNG Medical Media

The median duration of mechanical ventilation in survivors was 5 days in patients with mild ARDS, 7 days with moderate ARDS, and 9 days with severe ARDS, said Dr. Ferguson, director of critical care medicine at the University of Toronto. The study was published online May 21 in JAMA (doi: 10.1001/jama.2012.5669).

The European Society of Intensive Care Medicine convened the panel of experts in Berlin in 2011 to draft a new definition of ARDS in hopes of improving upon the 1994 definition from the American-European Consensus Conference (AECC), said Dr. Rubenfeld, professor of medicine at the University of Toronto and chief of the program in trauma/emergency and critical care at Sunnybrook Health Sciences Center, Toronto. Since the AECC definition was adopted widely, issues of reliability and validity have emerged. The American Thoracic Society and the Society of Critical Care Medicine endorsed the 2011 consensus effort.

Under the new Berlin Definition, patients with mild ARDS have mild hypoxemia, defined as a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen of 201-300 mm Hg (PaO₂/FIO₂ = 201-300 mm Hg). Moderate hypoxia (PaO₂/FIO₂ = 101-200 mm Hg) defines moderate ARDS, and severe hypoxia (PaO₂/FIO₂ = 100 mm Hg or less) defines severe ARDS.

The initial draft of the Berlin Definition included four ancillary variables for severe ARDS that were dropped after the meta-analysis found that they did not improve the predictive value for mortality, the speakers and their associates in the study reported. The abandoned variables were radiographic severity, respiratory system compliance, positive end-expiratory pressure, and corrected expired volume per minute.

Dr. Rubenfeld stressed that these variables still are important for clinicians to measure and for understanding ARDS, but they were not included in the definition of severe ARDS because they made the definition more complex while not adding anything to the predictive value of the definition.

He also cautioned that neither the Berlin Definition nor the AECC definition is designed to be a prognostic model; the end point of mortality was used to hone the Berlin Definition.

The Berlin Definition had better predictive validity for mortality than the AECC definition in an analysis using the area under the receiver operating curve (AUROC) in logistic regression models. The Berlin Definition had an AUROC of 0.577, compared with 0.536 for the AECC definition, a statistically significant improvement.

The data for the meta-analysis came from four multicenter clinical studies and three single-center physiological studies, the investigators reported.

Twenty-two percent of patients met the Berlin Definition criteria for mild ARDS, 50% had moderate ARDS, and 28% had severe ARDS. Median ventilator-free days declined with severity of disease, from 20 days with mild ARDS to 16 days with moderate ARDS and 1 day with severe ARDS.

Among patients with mild ARDS at baseline under the Berlin Definition, 29% progressed to moderate disease and 4% progressed to severe disease within 7 days. Among patients with moderate ARDS at baseline, 13% progressed to severe disease within 7 days.

Sherry Boschert/IMNG Medical Media

The investigators suggested that this approach of combining consensus discussions with empirical evaluation might be a model for creating more accurate, evidence-based definitions for critical illness syndromes. Previous ARDS definitions relied on expert consensus alone.

Without the empirical evaluation that led to deleting the ancillary variables, a needlessly complex ARDS definition would have been proposed, Dr. Rubenfeld said.

The study was sponsored by the European Society of Intensive Care Medicine, the National Institutes of Health, and the Canadian Institutes of Health Research (CIHR). CareFusion provided in-kind support for the study. Dr. Ferguson was supported by a CIHR New Investigator Award. Dr. Rubenfeld reported having financial relationships with Ikaria, Faron, and Cerus. Some of his associates in the study reported financial relationships with Maquet Medical, Hemodec, Faron, AstraZeneca, U.S. Biotest, Sirius Genetics, Sanofi-Aventis, Immunetrics, Abbott, Eli Lilly, Ikaria, GlaxoSmithKline, Tarix, Apeiron, and/or Novalung.

The Berlin Definition of ARDS

• Timing: Within 1 week of a known clinical insult or new or worsening respiratory symptoms.

• Chest imaging: Bilateral opacities on x-ray or CT scan not fully explained by effusions, lobar/lung collapse, or nodules.

• Origin of edema: Respiratory failure not fully explained by cardiac failure or fluid overload. Need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present.

• Oxygenation:

Mild: PaO₂/FIO₂ of 201-300 mm Hg with positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) of 5 cm H₂O or greater.

Moderate: PaO₂/FIO₂ of 101-200 mm Hg with PEEP of 5 cm H₂O or greater.

Severe: PaO₂/FIO₂ of 100 mm Hg or less with PEEP of 5 cm H₂O or greater.

If the altitude is higher than 1,000 m, the correction factor should be calculated as PaO₂/RO₂ × (barometric pressure/760).

SAN FRANCISCO – A proposed new definition of acute respiratory distress syndrome describes categories based on mild, moderate, or severe hypoxemia that correlate increasing severity with significantly increased mortality or increased time on mechanical ventilation among survivors.

The draft definition, created under consensus process by an international panel of experts, was refined by empirical testing in a meta-analysis of data on 4,457 patients in two large data sets from seven centers. The risk of mortality from acute respiratory distress syndrome (ARDS) was 27% with mild disease, 32% with moderate ARDS, and 45% with severe ARDS, Dr. Niall D. Ferguson and Dr. Gordon D. Rubenfeld reported at an international conference of the American Thoracic Society.

Sherry Boschert/IMNG Medical Media

The median duration of mechanical ventilation in survivors was 5 days in patients with mild ARDS, 7 days with moderate ARDS, and 9 days with severe ARDS, said Dr. Ferguson, director of critical care medicine at the University of Toronto. The study was published online May 21 in JAMA (doi: 10.1001/jama.2012.5669).

The European Society of Intensive Care Medicine convened the panel of experts in Berlin in 2011 to draft a new definition of ARDS in hopes of improving upon the 1994 definition from the American-European Consensus Conference (AECC), said Dr. Rubenfeld, professor of medicine at the University of Toronto and chief of the program in trauma/emergency and critical care at Sunnybrook Health Sciences Center, Toronto. Since the AECC definition was adopted widely, issues of reliability and validity have emerged. The American Thoracic Society and the Society of Critical Care Medicine endorsed the 2011 consensus effort.

Under the new Berlin Definition, patients with mild ARDS have mild hypoxemia, defined as a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen of 201-300 mm Hg (PaO₂/FIO₂ = 201-300 mm Hg). Moderate hypoxia (PaO₂/FIO₂ = 101-200 mm Hg) defines moderate ARDS, and severe hypoxia (PaO₂/FIO₂ = 100 mm Hg or less) defines severe ARDS.

The initial draft of the Berlin Definition included four ancillary variables for severe ARDS that were dropped after the meta-analysis found that they did not improve the predictive value for mortality, the speakers and their associates in the study reported. The abandoned variables were radiographic severity, respiratory system compliance, positive end-expiratory pressure, and corrected expired volume per minute.

Dr. Rubenfeld stressed that these variables still are important for clinicians to measure and for understanding ARDS, but they were not included in the definition of severe ARDS because they made the definition more complex while not adding anything to the predictive value of the definition.

He also cautioned that neither the Berlin Definition nor the AECC definition is designed to be a prognostic model; the end point of mortality was used to hone the Berlin Definition.

The Berlin Definition had better predictive validity for mortality than the AECC definition in an analysis using the area under the receiver operating curve (AUROC) in logistic regression models. The Berlin Definition had an AUROC of 0.577, compared with 0.536 for the AECC definition, a statistically significant improvement.

The data for the meta-analysis came from four multicenter clinical studies and three single-center physiological studies, the investigators reported.

Twenty-two percent of patients met the Berlin Definition criteria for mild ARDS, 50% had moderate ARDS, and 28% had severe ARDS. Median ventilator-free days declined with severity of disease, from 20 days with mild ARDS to 16 days with moderate ARDS and 1 day with severe ARDS.

Among patients with mild ARDS at baseline under the Berlin Definition, 29% progressed to moderate disease and 4% progressed to severe disease within 7 days. Among patients with moderate ARDS at baseline, 13% progressed to severe disease within 7 days.

Sherry Boschert/IMNG Medical Media

The investigators suggested that this approach of combining consensus discussions with empirical evaluation might be a model for creating more accurate, evidence-based definitions for critical illness syndromes. Previous ARDS definitions relied on expert consensus alone.

Without the empirical evaluation that led to deleting the ancillary variables, a needlessly complex ARDS definition would have been proposed, Dr. Rubenfeld said.

The study was sponsored by the European Society of Intensive Care Medicine, the National Institutes of Health, and the Canadian Institutes of Health Research (CIHR). CareFusion provided in-kind support for the study. Dr. Ferguson was supported by a CIHR New Investigator Award. Dr. Rubenfeld reported having financial relationships with Ikaria, Faron, and Cerus. Some of his associates in the study reported financial relationships with Maquet Medical, Hemodec, Faron, AstraZeneca, U.S. Biotest, Sirius Genetics, Sanofi-Aventis, Immunetrics, Abbott, Eli Lilly, Ikaria, GlaxoSmithKline, Tarix, Apeiron, and/or Novalung.

The Berlin Definition of ARDS

• Timing: Within 1 week of a known clinical insult or new or worsening respiratory symptoms.

• Chest imaging: Bilateral opacities on x-ray or CT scan not fully explained by effusions, lobar/lung collapse, or nodules.

• Origin of edema: Respiratory failure not fully explained by cardiac failure or fluid overload. Need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present.

• Oxygenation:

Mild: PaO₂/FIO₂ of 201-300 mm Hg with positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) of 5 cm H₂O or greater.

Moderate: PaO₂/FIO₂ of 101-200 mm Hg with PEEP of 5 cm H₂O or greater.

Severe: PaO₂/FIO₂ of 100 mm Hg or less with PEEP of 5 cm H₂O or greater.

If the altitude is higher than 1,000 m, the correction factor should be calculated as PaO₂/RO₂ × (barometric pressure/760).

SAN FRANCISCO – A proposed new definition of acute respiratory distress syndrome describes categories based on mild, moderate, or severe hypoxemia that correlate increasing severity with significantly increased mortality or increased time on mechanical ventilation among survivors.

The draft definition, created under consensus process by an international panel of experts, was refined by empirical testing in a meta-analysis of data on 4,457 patients in two large data sets from seven centers. The risk of mortality from acute respiratory distress syndrome (ARDS) was 27% with mild disease, 32% with moderate ARDS, and 45% with severe ARDS, Dr. Niall D. Ferguson and Dr. Gordon D. Rubenfeld reported at an international conference of the American Thoracic Society.

Sherry Boschert/IMNG Medical Media

The median duration of mechanical ventilation in survivors was 5 days in patients with mild ARDS, 7 days with moderate ARDS, and 9 days with severe ARDS, said Dr. Ferguson, director of critical care medicine at the University of Toronto. The study was published online May 21 in JAMA (doi: 10.1001/jama.2012.5669).

The European Society of Intensive Care Medicine convened the panel of experts in Berlin in 2011 to draft a new definition of ARDS in hopes of improving upon the 1994 definition from the American-European Consensus Conference (AECC), said Dr. Rubenfeld, professor of medicine at the University of Toronto and chief of the program in trauma/emergency and critical care at Sunnybrook Health Sciences Center, Toronto. Since the AECC definition was adopted widely, issues of reliability and validity have emerged. The American Thoracic Society and the Society of Critical Care Medicine endorsed the 2011 consensus effort.

Under the new Berlin Definition, patients with mild ARDS have mild hypoxemia, defined as a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen of 201-300 mm Hg (PaO₂/FIO₂ = 201-300 mm Hg). Moderate hypoxia (PaO₂/FIO₂ = 101-200 mm Hg) defines moderate ARDS, and severe hypoxia (PaO₂/FIO₂ = 100 mm Hg or less) defines severe ARDS.

The initial draft of the Berlin Definition included four ancillary variables for severe ARDS that were dropped after the meta-analysis found that they did not improve the predictive value for mortality, the speakers and their associates in the study reported. The abandoned variables were radiographic severity, respiratory system compliance, positive end-expiratory pressure, and corrected expired volume per minute.

Dr. Rubenfeld stressed that these variables still are important for clinicians to measure and for understanding ARDS, but they were not included in the definition of severe ARDS because they made the definition more complex while not adding anything to the predictive value of the definition.

He also cautioned that neither the Berlin Definition nor the AECC definition is designed to be a prognostic model; the end point of mortality was used to hone the Berlin Definition.

The Berlin Definition had better predictive validity for mortality than the AECC definition in an analysis using the area under the receiver operating curve (AUROC) in logistic regression models. The Berlin Definition had an AUROC of 0.577, compared with 0.536 for the AECC definition, a statistically significant improvement.

The data for the meta-analysis came from four multicenter clinical studies and three single-center physiological studies, the investigators reported.

Twenty-two percent of patients met the Berlin Definition criteria for mild ARDS, 50% had moderate ARDS, and 28% had severe ARDS. Median ventilator-free days declined with severity of disease, from 20 days with mild ARDS to 16 days with moderate ARDS and 1 day with severe ARDS.

Among patients with mild ARDS at baseline under the Berlin Definition, 29% progressed to moderate disease and 4% progressed to severe disease within 7 days. Among patients with moderate ARDS at baseline, 13% progressed to severe disease within 7 days.

Sherry Boschert/IMNG Medical Media

The investigators suggested that this approach of combining consensus discussions with empirical evaluation might be a model for creating more accurate, evidence-based definitions for critical illness syndromes. Previous ARDS definitions relied on expert consensus alone.

Without the empirical evaluation that led to deleting the ancillary variables, a needlessly complex ARDS definition would have been proposed, Dr. Rubenfeld said.

The study was sponsored by the European Society of Intensive Care Medicine, the National Institutes of Health, and the Canadian Institutes of Health Research (CIHR). CareFusion provided in-kind support for the study. Dr. Ferguson was supported by a CIHR New Investigator Award. Dr. Rubenfeld reported having financial relationships with Ikaria, Faron, and Cerus. Some of his associates in the study reported financial relationships with Maquet Medical, Hemodec, Faron, AstraZeneca, U.S. Biotest, Sirius Genetics, Sanofi-Aventis, Immunetrics, Abbott, Eli Lilly, Ikaria, GlaxoSmithKline, Tarix, Apeiron, and/or Novalung.

The Berlin Definition of ARDS

• Timing: Within 1 week of a known clinical insult or new or worsening respiratory symptoms.

• Chest imaging: Bilateral opacities on x-ray or CT scan not fully explained by effusions, lobar/lung collapse, or nodules.

• Origin of edema: Respiratory failure not fully explained by cardiac failure or fluid overload. Need objective assessment (e.g., echocardiography) to exclude hydrostatic edema if no risk factor present.

• Oxygenation:

Mild: PaO₂/FIO₂ of 201-300 mm Hg with positive end-expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) of 5 cm H₂O or greater.

Moderate: PaO₂/FIO₂ of 101-200 mm Hg with PEEP of 5 cm H₂O or greater.

Severe: PaO₂/FIO₂ of 100 mm Hg or less with PEEP of 5 cm H₂O or greater.

If the altitude is higher than 1,000 m, the correction factor should be calculated as PaO₂/RO₂ × (barometric pressure/760).

SAN FRANCISCO – Patients aged 55-74 years who have at least a 30 pack-year smoking history should be offered annual low-dose CT lung cancer screening, even if they have quit within the past 15 years, according to a systematic review published online May 20 in JAMA.

The review forms the basis of the new lung cancer screening clinical practice guidelines from the American College of Chest Physicians and the American Society of Clinical Oncology. The recommendations are based largely on the 53,454-patient, randomized NLST (National Lung Screening Trial), which found that for every 1,000 high-risk smokers, three rounds of annual CT screening saved approximately three lives over about 7 years, which is comparable, at least, to the absolute benefit of screening mammographies in older women (N. Engl. J. Med. 2011;365:395-409).

The risks – including misdiagnosis and unnecessary surgery – and potential benefits should be explained to patients before they opt for screening. "People need to know" that "19 out of 20 positive results are going to be false positive. A positive screen does not equal a diagnosis of lung cancer," said coauthor Dr. Michael K. Gould, assistant director for health services research at Kaiser Permanente of Southern California, Pasadena.

In addition, "CT screening should not be performed" in smokers and ex-smokers who fall outside of the high-risk group, or in those with severe comorbidities that limit life expectancy or preclude treatment, according to the guidelines (JAMA 2012 May 20 [doi:10.1001/jama.2012.5521]).

The risks and benefits of screening are just "too close to call" for those patients, said lead author Dr. Peter Bach, director of the center for health policy and outcomes at Memorial Sloan-Kettering Cancer Center in New York.

After an extensive literature review, the researchers included eight randomized trials and 13 cohort studies in its final analysis. Although they are confident that screening benefits high-risk patients – based mostly on the NLST, with some added input from smaller trials – they are also concerned about the lack of data on the potential harms of screening, which led to the recommendation to offer screening only to high-risk patients, Dr. Bach said.

Overall, the lack of additional research led both recommendations to be characterized as "weak" under the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.

The impact of screening even high-risk patients "on smoking cessation, quality of life, and cost-effectiveness is really quite unclear. We don’t know in any sense what the frequency should be or the duration," Dr. Bach said.

Also unclear is how screening will play out in settings less rigorous than the academic centers where the NLST was conducted. Patient compliance with screening at those centers was 90%, adverse events were rare, and subsequent diagnostic work-ups and interventions were available.

To mitigate potential problems, the guidelines recommend that screening be done in similar multidisciplinary settings.

The authors also call for a screening registry "that records each patient’s experience [to] help us develop a quality measurement system similar to mammography screening that could maximize the benefits and minimize the harm for individuals who undergo screening," Dr. Bach said.

A supplement to the JAMA article includes a section entitled "Components of a Conversation About CT Screening," which addresses how to talk with patients about these issues.

The American Thoracic Society has endorsed the guidelines.

Dr. Bach reported that he has received speaking fees from Genentech. Coauthors reported ties to pharmaceutical companies such as Oncimmune and governmental agencies such as the National Cancer Institute. Dr. Gould and Dr. Bauchner said they have no relevant disclosures.

SAN FRANCISCO – Patients aged 55-74 years who have at least a 30 pack-year smoking history should be offered annual low-dose CT lung cancer screening, even if they have quit within the past 15 years, according to a systematic review published online May 20 in JAMA.

The review forms the basis of the new lung cancer screening clinical practice guidelines from the American College of Chest Physicians and the American Society of Clinical Oncology. The recommendations are based largely on the 53,454-patient, randomized NLST (National Lung Screening Trial), which found that for every 1,000 high-risk smokers, three rounds of annual CT screening saved approximately three lives over about 7 years, which is comparable, at least, to the absolute benefit of screening mammographies in older women (N. Engl. J. Med. 2011;365:395-409).

The risks – including misdiagnosis and unnecessary surgery – and potential benefits should be explained to patients before they opt for screening. "People need to know" that "19 out of 20 positive results are going to be false positive. A positive screen does not equal a diagnosis of lung cancer," said coauthor Dr. Michael K. Gould, assistant director for health services research at Kaiser Permanente of Southern California, Pasadena.

In addition, "CT screening should not be performed" in smokers and ex-smokers who fall outside of the high-risk group, or in those with severe comorbidities that limit life expectancy or preclude treatment, according to the guidelines (JAMA 2012 May 20 [doi:10.1001/jama.2012.5521]).

The risks and benefits of screening are just "too close to call" for those patients, said lead author Dr. Peter Bach, director of the center for health policy and outcomes at Memorial Sloan-Kettering Cancer Center in New York.

After an extensive literature review, the researchers included eight randomized trials and 13 cohort studies in its final analysis. Although they are confident that screening benefits high-risk patients – based mostly on the NLST, with some added input from smaller trials – they are also concerned about the lack of data on the potential harms of screening, which led to the recommendation to offer screening only to high-risk patients, Dr. Bach said.

Overall, the lack of additional research led both recommendations to be characterized as "weak" under the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.

The impact of screening even high-risk patients "on smoking cessation, quality of life, and cost-effectiveness is really quite unclear. We don’t know in any sense what the frequency should be or the duration," Dr. Bach said.

Also unclear is how screening will play out in settings less rigorous than the academic centers where the NLST was conducted. Patient compliance with screening at those centers was 90%, adverse events were rare, and subsequent diagnostic work-ups and interventions were available.

To mitigate potential problems, the guidelines recommend that screening be done in similar multidisciplinary settings.

The authors also call for a screening registry "that records each patient’s experience [to] help us develop a quality measurement system similar to mammography screening that could maximize the benefits and minimize the harm for individuals who undergo screening," Dr. Bach said.

A supplement to the JAMA article includes a section entitled "Components of a Conversation About CT Screening," which addresses how to talk with patients about these issues.

The American Thoracic Society has endorsed the guidelines.

Dr. Bach reported that he has received speaking fees from Genentech. Coauthors reported ties to pharmaceutical companies such as Oncimmune and governmental agencies such as the National Cancer Institute. Dr. Gould and Dr. Bauchner said they have no relevant disclosures.

SAN FRANCISCO – Patients aged 55-74 years who have at least a 30 pack-year smoking history should be offered annual low-dose CT lung cancer screening, even if they have quit within the past 15 years, according to a systematic review published online May 20 in JAMA.

The review forms the basis of the new lung cancer screening clinical practice guidelines from the American College of Chest Physicians and the American Society of Clinical Oncology. The recommendations are based largely on the 53,454-patient, randomized NLST (National Lung Screening Trial), which found that for every 1,000 high-risk smokers, three rounds of annual CT screening saved approximately three lives over about 7 years, which is comparable, at least, to the absolute benefit of screening mammographies in older women (N. Engl. J. Med. 2011;365:395-409).

The risks – including misdiagnosis and unnecessary surgery – and potential benefits should be explained to patients before they opt for screening. "People need to know" that "19 out of 20 positive results are going to be false positive. A positive screen does not equal a diagnosis of lung cancer," said coauthor Dr. Michael K. Gould, assistant director for health services research at Kaiser Permanente of Southern California, Pasadena.

In addition, "CT screening should not be performed" in smokers and ex-smokers who fall outside of the high-risk group, or in those with severe comorbidities that limit life expectancy or preclude treatment, according to the guidelines (JAMA 2012 May 20 [doi:10.1001/jama.2012.5521]).

The risks and benefits of screening are just "too close to call" for those patients, said lead author Dr. Peter Bach, director of the center for health policy and outcomes at Memorial Sloan-Kettering Cancer Center in New York.

After an extensive literature review, the researchers included eight randomized trials and 13 cohort studies in its final analysis. Although they are confident that screening benefits high-risk patients – based mostly on the NLST, with some added input from smaller trials – they are also concerned about the lack of data on the potential harms of screening, which led to the recommendation to offer screening only to high-risk patients, Dr. Bach said.

Overall, the lack of additional research led both recommendations to be characterized as "weak" under the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system.

The impact of screening even high-risk patients "on smoking cessation, quality of life, and cost-effectiveness is really quite unclear. We don’t know in any sense what the frequency should be or the duration," Dr. Bach said.

Also unclear is how screening will play out in settings less rigorous than the academic centers where the NLST was conducted. Patient compliance with screening at those centers was 90%, adverse events were rare, and subsequent diagnostic work-ups and interventions were available.

To mitigate potential problems, the guidelines recommend that screening be done in similar multidisciplinary settings.

The authors also call for a screening registry "that records each patient’s experience [to] help us develop a quality measurement system similar to mammography screening that could maximize the benefits and minimize the harm for individuals who undergo screening," Dr. Bach said.

A supplement to the JAMA article includes a section entitled "Components of a Conversation About CT Screening," which addresses how to talk with patients about these issues.

The American Thoracic Society has endorsed the guidelines.

Dr. Bach reported that he has received speaking fees from Genentech. Coauthors reported ties to pharmaceutical companies such as Oncimmune and governmental agencies such as the National Cancer Institute. Dr. Gould and Dr. Bauchner said they have no relevant disclosures.