Pulmonary Health Hub

Nearly a third of patients have asthma exacerbation in the 2 years after medication step-down, according to a new study published in the September issue of Chest.

With the goal of using the least amount of medication to control asthma, guidelines recommend considering medication step-down after 3 months of stabilized asthma. However, there is limited evidence backing these recommendations, especially when it comes to understanding the long-term outcomes after asthma medication step-down.

Dr. Matthew A. Rank of the division of allergy, asthma, and clinical immunology at the Mayo Clinic in Scottsdale, Ariz., and colleagues analyzed the long-term outcomes of patients after asthma medication step-down.

©marekuliasz/thinkstockphotos.com

The investigators conducted a retrospective claims-based analysis using data obtained from the Optum Labs Data Warehouse which contains information from more than 100 million deidentified patients with Medicare Advantage or commercial insurance plans (Chest. 2015;148[3]:630-39). .

Data was extracted on patients who had an asthma diagnosis code between 2000 and 2012 with continuous medical and pharmacy coverage for 3 or more years during the study period and with a history of medication step-down.

Investigators defined a medication step-down as greater or equal to 50% decrease in asthma controller medication between evaluations. Stability was defined as not having an asthma exacerbation requiring care in the hospital or ED, or systemic corticosteroids and claiming fewer than two rescue inhalers prescriptions in the 4 month study period.

The study cohort was divided into four asthma stability groups: 0-3 months, 4-7 months, 8-11 months, and greater to or equal to 12 months of stability.

Of the 26,292 individuals included in the study, 32% developed an asthma exacerbation during the 2 years after medication step-down. There was a strong association between the risk of developing an asthma exacerbation during the 2-year study period and the length of asthma stability prior to medication step-down. For instance, 44% in participants with less than 4 months of stability, 34% with 4-7 months of stability, 30% with 8-11 months of stability, and 21% with more than 12 months of stability (P less than .001).

In addition, study participants who were women, were black, were younger than 19 years old, had a Charlson comorbidity index great than or equal to 1, and at least two outpatient visits for asthma were significantly associated with a shorter interval to asthma exacerbation (P less than.001 for all variables).

Finally, most study participants had a hospital or ED visit, systemic corticosteroids, two rescue inhalers in a 4-month period, or needed to return to baseline asthma controller treatment. The authors suggest that this is evidence that most of the cohort continued to have underlying asthma during the 2-year study period. Furthermore, 33% of participants with less than 4 months of stability required return to baseline treatment versus 8%, 13%, and 15% for more than 12 months of stability, 8-11 months, and 4-7 months, respectively.

Among the limitations noted by the authors: Data were from insured patients, data did not indicate if step-down involved consultation with a health care provider, and the cohort did not include patients who did not step-down as a comparison.

“Individuals and their providers can cautiously apply the data from this study to decisions about stepping down asthma medications. The novel insights from this analysis that contribute to this decision making process are consideration to the length of stability prior to step-down and the rate of asthma exacerbations in the 24 months following step-down,” the authors wrote.

The study was funded by the Mayo Foundation for Medical Education and Research. The authors report no disclosures.

Nearly a third of patients have asthma exacerbation in the 2 years after medication step-down, according to a new study published in the September issue of Chest.

With the goal of using the least amount of medication to control asthma, guidelines recommend considering medication step-down after 3 months of stabilized asthma. However, there is limited evidence backing these recommendations, especially when it comes to understanding the long-term outcomes after asthma medication step-down.

Dr. Matthew A. Rank of the division of allergy, asthma, and clinical immunology at the Mayo Clinic in Scottsdale, Ariz., and colleagues analyzed the long-term outcomes of patients after asthma medication step-down.

©marekuliasz/thinkstockphotos.com

The investigators conducted a retrospective claims-based analysis using data obtained from the Optum Labs Data Warehouse which contains information from more than 100 million deidentified patients with Medicare Advantage or commercial insurance plans (Chest. 2015;148[3]:630-39). .

Data was extracted on patients who had an asthma diagnosis code between 2000 and 2012 with continuous medical and pharmacy coverage for 3 or more years during the study period and with a history of medication step-down.

Investigators defined a medication step-down as greater or equal to 50% decrease in asthma controller medication between evaluations. Stability was defined as not having an asthma exacerbation requiring care in the hospital or ED, or systemic corticosteroids and claiming fewer than two rescue inhalers prescriptions in the 4 month study period.

The study cohort was divided into four asthma stability groups: 0-3 months, 4-7 months, 8-11 months, and greater to or equal to 12 months of stability.

Of the 26,292 individuals included in the study, 32% developed an asthma exacerbation during the 2 years after medication step-down. There was a strong association between the risk of developing an asthma exacerbation during the 2-year study period and the length of asthma stability prior to medication step-down. For instance, 44% in participants with less than 4 months of stability, 34% with 4-7 months of stability, 30% with 8-11 months of stability, and 21% with more than 12 months of stability (P less than .001).

In addition, study participants who were women, were black, were younger than 19 years old, had a Charlson comorbidity index great than or equal to 1, and at least two outpatient visits for asthma were significantly associated with a shorter interval to asthma exacerbation (P less than.001 for all variables).

Finally, most study participants had a hospital or ED visit, systemic corticosteroids, two rescue inhalers in a 4-month period, or needed to return to baseline asthma controller treatment. The authors suggest that this is evidence that most of the cohort continued to have underlying asthma during the 2-year study period. Furthermore, 33% of participants with less than 4 months of stability required return to baseline treatment versus 8%, 13%, and 15% for more than 12 months of stability, 8-11 months, and 4-7 months, respectively.

Among the limitations noted by the authors: Data were from insured patients, data did not indicate if step-down involved consultation with a health care provider, and the cohort did not include patients who did not step-down as a comparison.

“Individuals and their providers can cautiously apply the data from this study to decisions about stepping down asthma medications. The novel insights from this analysis that contribute to this decision making process are consideration to the length of stability prior to step-down and the rate of asthma exacerbations in the 24 months following step-down,” the authors wrote.

The study was funded by the Mayo Foundation for Medical Education and Research. The authors report no disclosures.

Nearly a third of patients have asthma exacerbation in the 2 years after medication step-down, according to a new study published in the September issue of Chest.

With the goal of using the least amount of medication to control asthma, guidelines recommend considering medication step-down after 3 months of stabilized asthma. However, there is limited evidence backing these recommendations, especially when it comes to understanding the long-term outcomes after asthma medication step-down.

Dr. Matthew A. Rank of the division of allergy, asthma, and clinical immunology at the Mayo Clinic in Scottsdale, Ariz., and colleagues analyzed the long-term outcomes of patients after asthma medication step-down.

©marekuliasz/thinkstockphotos.com

The investigators conducted a retrospective claims-based analysis using data obtained from the Optum Labs Data Warehouse which contains information from more than 100 million deidentified patients with Medicare Advantage or commercial insurance plans (Chest. 2015;148[3]:630-39). .

Data was extracted on patients who had an asthma diagnosis code between 2000 and 2012 with continuous medical and pharmacy coverage for 3 or more years during the study period and with a history of medication step-down.

Investigators defined a medication step-down as greater or equal to 50% decrease in asthma controller medication between evaluations. Stability was defined as not having an asthma exacerbation requiring care in the hospital or ED, or systemic corticosteroids and claiming fewer than two rescue inhalers prescriptions in the 4 month study period.

The study cohort was divided into four asthma stability groups: 0-3 months, 4-7 months, 8-11 months, and greater to or equal to 12 months of stability.

Of the 26,292 individuals included in the study, 32% developed an asthma exacerbation during the 2 years after medication step-down. There was a strong association between the risk of developing an asthma exacerbation during the 2-year study period and the length of asthma stability prior to medication step-down. For instance, 44% in participants with less than 4 months of stability, 34% with 4-7 months of stability, 30% with 8-11 months of stability, and 21% with more than 12 months of stability (P less than .001).

In addition, study participants who were women, were black, were younger than 19 years old, had a Charlson comorbidity index great than or equal to 1, and at least two outpatient visits for asthma were significantly associated with a shorter interval to asthma exacerbation (P less than.001 for all variables).

Finally, most study participants had a hospital or ED visit, systemic corticosteroids, two rescue inhalers in a 4-month period, or needed to return to baseline asthma controller treatment. The authors suggest that this is evidence that most of the cohort continued to have underlying asthma during the 2-year study period. Furthermore, 33% of participants with less than 4 months of stability required return to baseline treatment versus 8%, 13%, and 15% for more than 12 months of stability, 8-11 months, and 4-7 months, respectively.

Among the limitations noted by the authors: Data were from insured patients, data did not indicate if step-down involved consultation with a health care provider, and the cohort did not include patients who did not step-down as a comparison.

“Individuals and their providers can cautiously apply the data from this study to decisions about stepping down asthma medications. The novel insights from this analysis that contribute to this decision making process are consideration to the length of stability prior to step-down and the rate of asthma exacerbations in the 24 months following step-down,” the authors wrote.

The study was funded by the Mayo Foundation for Medical Education and Research. The authors report no disclosures.

The cost burden of chronic obstructive pulmonary disease increased significantly between 2000 and 2010 in British Columbia, according to results from a Canadian cohort study.

Hospitalization – and the fact that more COPD patients were diagnosed in the hospital rather than in community settings – appeared to be the primary driver of excess costs in COPD patients, which were about $5,452 more per patient-year than for a matched comparison cohort of people without COPD. (Note: All dollar amounts are in Canadian dollars, which were valued at 95% of the U.S. dollar in 2010).

©designer491/Thinkstockphotos.com

Excess costs related to COPD increased by $296 per person year (P less than .01) over the course of the study, with hospital costs accounting for the great majority, increasing by $258 per person-year (P less than .01).

Inpatient costs accounted for more than half (57%) of total excess COPD-related costs recorded, with more than 40% of people in the COPD cohort diagnosed after hospital admission.

The study authors, led by Amir Khakban, M.Sc, of the University of British Colombia in Vancouver, suggested that low rates of spirometry use and limited awareness of COPD among community practitioners were the key factors leading to more hospitalizations over the course of a decade, and consequently to higher costs.

For their research, published in the September issue of CHEST (2015;148[3]:640-46), Mr. Khakban and colleagues used health care billing records from 153,570 COPD patients in British Columbia along with 246,801 age- and sex-matched controls identified in the same government database. Mean age at entry was 66.9 years for both cohorts, and slightly under half of the patients were women.

COPD is a known contributor to high medical costs, due to disease exacerbations that require hospitalization, and has long been recognized in Canada and elsewhere as a leading cause of hospitalization (Respir Med. 2003;97[suppl C]:S23-S31). However, Mr. Khakban and colleagues’ study showed a rapid cost increase over a 10-year period, with costs 38% higher in 2010 than in 2001.

Compared with hospital-related costs (at 57%), outpatient, medication, and community care costs accounted for 16%, 22%, and 5%, respectively, of the excess costs seen among COPD patients in the study.

“Despite improvements, current disease management and care standards seem to be far from optimal and are not likely making any major impact,” the investigators wrote in their analysis. “This is especially evident in the high and growing rate of hospitalization as a major determinant of the burden of COPD.”

Mr. Khakban and colleagues noted that their findings likely represent an underestimate of the true cost burden of COPD, as reliance on narrow definitions from medical billing records means many cases were likely to have been missed. Also, they noted, the database used did not capture information on lung function or smoking, so costs could not be further analyzed according to disease severity or smoking status.

“In addition, not all components of direct costs are captured in the administrative health data. For example, costs of nonprescription medication or devices, and costs of complementary and alternative care are not captured in our results.”

The study was funded by the Institute for Heart + Lung Health, Genome Canada, St. Paul’s Hospital Foundation, PROOF Centre, the National Sanitarium Association, and the Canadian Respiratory Research Network. One coauthor, Carlo Marra, Pharm.D., disclosed financial relationships with GlaxoSmithKline, Pfizer and Abbvie.

The cost burden of chronic obstructive pulmonary disease increased significantly between 2000 and 2010 in British Columbia, according to results from a Canadian cohort study.

Hospitalization – and the fact that more COPD patients were diagnosed in the hospital rather than in community settings – appeared to be the primary driver of excess costs in COPD patients, which were about $5,452 more per patient-year than for a matched comparison cohort of people without COPD. (Note: All dollar amounts are in Canadian dollars, which were valued at 95% of the U.S. dollar in 2010).

©designer491/Thinkstockphotos.com

Excess costs related to COPD increased by $296 per person year (P less than .01) over the course of the study, with hospital costs accounting for the great majority, increasing by $258 per person-year (P less than .01).

Inpatient costs accounted for more than half (57%) of total excess COPD-related costs recorded, with more than 40% of people in the COPD cohort diagnosed after hospital admission.

The study authors, led by Amir Khakban, M.Sc, of the University of British Colombia in Vancouver, suggested that low rates of spirometry use and limited awareness of COPD among community practitioners were the key factors leading to more hospitalizations over the course of a decade, and consequently to higher costs.

For their research, published in the September issue of CHEST (2015;148[3]:640-46), Mr. Khakban and colleagues used health care billing records from 153,570 COPD patients in British Columbia along with 246,801 age- and sex-matched controls identified in the same government database. Mean age at entry was 66.9 years for both cohorts, and slightly under half of the patients were women.

COPD is a known contributor to high medical costs, due to disease exacerbations that require hospitalization, and has long been recognized in Canada and elsewhere as a leading cause of hospitalization (Respir Med. 2003;97[suppl C]:S23-S31). However, Mr. Khakban and colleagues’ study showed a rapid cost increase over a 10-year period, with costs 38% higher in 2010 than in 2001.

Compared with hospital-related costs (at 57%), outpatient, medication, and community care costs accounted for 16%, 22%, and 5%, respectively, of the excess costs seen among COPD patients in the study.

“Despite improvements, current disease management and care standards seem to be far from optimal and are not likely making any major impact,” the investigators wrote in their analysis. “This is especially evident in the high and growing rate of hospitalization as a major determinant of the burden of COPD.”

Mr. Khakban and colleagues noted that their findings likely represent an underestimate of the true cost burden of COPD, as reliance on narrow definitions from medical billing records means many cases were likely to have been missed. Also, they noted, the database used did not capture information on lung function or smoking, so costs could not be further analyzed according to disease severity or smoking status.

“In addition, not all components of direct costs are captured in the administrative health data. For example, costs of nonprescription medication or devices, and costs of complementary and alternative care are not captured in our results.”

The study was funded by the Institute for Heart + Lung Health, Genome Canada, St. Paul’s Hospital Foundation, PROOF Centre, the National Sanitarium Association, and the Canadian Respiratory Research Network. One coauthor, Carlo Marra, Pharm.D., disclosed financial relationships with GlaxoSmithKline, Pfizer and Abbvie.

The cost burden of chronic obstructive pulmonary disease increased significantly between 2000 and 2010 in British Columbia, according to results from a Canadian cohort study.

Hospitalization – and the fact that more COPD patients were diagnosed in the hospital rather than in community settings – appeared to be the primary driver of excess costs in COPD patients, which were about $5,452 more per patient-year than for a matched comparison cohort of people without COPD. (Note: All dollar amounts are in Canadian dollars, which were valued at 95% of the U.S. dollar in 2010).

©designer491/Thinkstockphotos.com

Excess costs related to COPD increased by $296 per person year (P less than .01) over the course of the study, with hospital costs accounting for the great majority, increasing by $258 per person-year (P less than .01).

Inpatient costs accounted for more than half (57%) of total excess COPD-related costs recorded, with more than 40% of people in the COPD cohort diagnosed after hospital admission.

The study authors, led by Amir Khakban, M.Sc, of the University of British Colombia in Vancouver, suggested that low rates of spirometry use and limited awareness of COPD among community practitioners were the key factors leading to more hospitalizations over the course of a decade, and consequently to higher costs.

For their research, published in the September issue of CHEST (2015;148[3]:640-46), Mr. Khakban and colleagues used health care billing records from 153,570 COPD patients in British Columbia along with 246,801 age- and sex-matched controls identified in the same government database. Mean age at entry was 66.9 years for both cohorts, and slightly under half of the patients were women.

COPD is a known contributor to high medical costs, due to disease exacerbations that require hospitalization, and has long been recognized in Canada and elsewhere as a leading cause of hospitalization (Respir Med. 2003;97[suppl C]:S23-S31). However, Mr. Khakban and colleagues’ study showed a rapid cost increase over a 10-year period, with costs 38% higher in 2010 than in 2001.

Compared with hospital-related costs (at 57%), outpatient, medication, and community care costs accounted for 16%, 22%, and 5%, respectively, of the excess costs seen among COPD patients in the study.

“Despite improvements, current disease management and care standards seem to be far from optimal and are not likely making any major impact,” the investigators wrote in their analysis. “This is especially evident in the high and growing rate of hospitalization as a major determinant of the burden of COPD.”

Mr. Khakban and colleagues noted that their findings likely represent an underestimate of the true cost burden of COPD, as reliance on narrow definitions from medical billing records means many cases were likely to have been missed. Also, they noted, the database used did not capture information on lung function or smoking, so costs could not be further analyzed according to disease severity or smoking status.

“In addition, not all components of direct costs are captured in the administrative health data. For example, costs of nonprescription medication or devices, and costs of complementary and alternative care are not captured in our results.”

The study was funded by the Institute for Heart + Lung Health, Genome Canada, St. Paul’s Hospital Foundation, PROOF Centre, the National Sanitarium Association, and the Canadian Respiratory Research Network. One coauthor, Carlo Marra, Pharm.D., disclosed financial relationships with GlaxoSmithKline, Pfizer and Abbvie.

DENVER – Adding the antiangiogenic antibody bevacizumab to chemotherapy improves outcomes in patients who have unresectable mesothelioma, with little downside, according to results of MAPS (the Mesothelioma Avastin Plus Pemetrexed-Cisplatin Study).

Median overall survival in the multicenter randomized phase III trial was 2.75 months longer for patients given bevacizumab in addition to the doublet of pemetrexed plus cisplatin, first author Dr. Arnaud Scherpereel reported at a world conference on lung cancer. This benefit was achieved with only a small increase in the rate of grade 3 or 4 toxicity and no detriment to quality of life.

“We feel that the treatment of pemetrexed-cisplatin with bevacizumab is a new treatment paradigm for mesothelioma patients eligible for bevacizumab and not candidates for curative surgery. And I think that most of them may be eligible for this drug because these patients are not so often smokers and [have] lung conservation, they have less comorbidities,” he said. “Perhaps this treatment may be accepted as a new standard of care for these patients.”

The control arm had much better survival than had been seen historically with this chemotherapy, noted Dr. Scherpereel, who is head of the pulmonary and thoracic oncology department and a professor at the University Hospital (CHRU) of Lille, France. This may have been because of the trial’s eligibility criteria, chosen to ensure that patients could receive bevacizumab, or to the facts that patients had to be fit enough to undergo thoracoscopy and that some received pleurodesis before enrollment.

Bevacizumab benefit may therefore differ in other patients, he acknowledged. “We will see in the real life. I hope first to have the drug [available] for this indication,” he said an the conference sponsored by the International Association for the Study of Lung Cancer.

Press conference moderator Dr. James R. Jett, conference cochair and a professor of medicine at National Jewish Health in Denver, noted that pemetrexed-cisplatin remains the standard of care in the United States. “We don’t have bevacizumab as the standard, but this [trial] may very well change that,” he said.

He wondered if the unusually good outcomes in the control arm were related to earlier diagnosis, but said that regardless, bevacizumab still showed a benefit. “I think the main message here is that it’s important to do concurrent controls because if we were comparing to a historic control, it would be very difficult,” he said.

MAPS was sponsored by the French Cooperative Thoracic Intergroup and was open to patients with mesothelioma who were not candidates for surgery and had not received chemotherapy. Those who had pleural effusion were allowed to undergo a talc pleurodesis at the time of diagnostic thoracoscopy.

A total of 448 patients were randomized to open-label cisplatin and pemetrexed, with versus without bevacizumab (Avastin). The bevacizumab group additionally received the drug alone as maintenance therapy after completing chemotherapy. Cross-over was not allowed.

With a median follow-up of 39.4 months, the bevacizumab arm had better median overall survival (18.82 vs. 16.07 months; hazard ratio, 0.76; P = .015)—the trial’s primary endpoint—and progression-free survival (9.59 vs. 7.48 months; hazard ratio, 0.61; P less than .0001).

“Usually the progression-free survival in the trials with best medical treatment was between 6 and 7 months,” Dr. Scherpereel pointed out. Similarly, “the best [overall survival] results with the standard treatment is close to 13 months.”

“There was no significant difference between the two arms in the percentage of drug delivery or the percentage of patients having second-line treatment which could explain the increase of survival in the bevacizumab arm,” he reported.

The proportion of patients experiencing grade 3 or 4 toxicity was higher with bevacizumab (71.2% vs. 62.1%; P = .04), largely because of more nonhematologic toxicity such as hypertension and venous thromboembolism. However, this additional toxicity was manageable, according to Dr. Scherpereel.

Furthermore, in terms of quality of life measures, patients in the bevacizumab arm had a greater improvement in fatigue from baseline (P = .046) and scores for other measures did not differ between arms.

“We did not find some predictive clinical or biological marker [of bevacizumab benefit] for this study,” he said. In particular, patients’ pretreatment levels of vascular endothelial growth factor (VEGF) did not identify a group more likely to benefit. But an ongoing companion study is still evaluating other biomarkers, such as mesothelin and endocan, he added.

Dr. Scherpereel disclosed that he and coinvestigators had affiliations with Roche and other companies. Roche supplied bevacizumab and a research grant for the biomarker studies.

DENVER – Adding the antiangiogenic antibody bevacizumab to chemotherapy improves outcomes in patients who have unresectable mesothelioma, with little downside, according to results of MAPS (the Mesothelioma Avastin Plus Pemetrexed-Cisplatin Study).

Median overall survival in the multicenter randomized phase III trial was 2.75 months longer for patients given bevacizumab in addition to the doublet of pemetrexed plus cisplatin, first author Dr. Arnaud Scherpereel reported at a world conference on lung cancer. This benefit was achieved with only a small increase in the rate of grade 3 or 4 toxicity and no detriment to quality of life.

“We feel that the treatment of pemetrexed-cisplatin with bevacizumab is a new treatment paradigm for mesothelioma patients eligible for bevacizumab and not candidates for curative surgery. And I think that most of them may be eligible for this drug because these patients are not so often smokers and [have] lung conservation, they have less comorbidities,” he said. “Perhaps this treatment may be accepted as a new standard of care for these patients.”

The control arm had much better survival than had been seen historically with this chemotherapy, noted Dr. Scherpereel, who is head of the pulmonary and thoracic oncology department and a professor at the University Hospital (CHRU) of Lille, France. This may have been because of the trial’s eligibility criteria, chosen to ensure that patients could receive bevacizumab, or to the facts that patients had to be fit enough to undergo thoracoscopy and that some received pleurodesis before enrollment.

Bevacizumab benefit may therefore differ in other patients, he acknowledged. “We will see in the real life. I hope first to have the drug [available] for this indication,” he said an the conference sponsored by the International Association for the Study of Lung Cancer.

Press conference moderator Dr. James R. Jett, conference cochair and a professor of medicine at National Jewish Health in Denver, noted that pemetrexed-cisplatin remains the standard of care in the United States. “We don’t have bevacizumab as the standard, but this [trial] may very well change that,” he said.

He wondered if the unusually good outcomes in the control arm were related to earlier diagnosis, but said that regardless, bevacizumab still showed a benefit. “I think the main message here is that it’s important to do concurrent controls because if we were comparing to a historic control, it would be very difficult,” he said.

MAPS was sponsored by the French Cooperative Thoracic Intergroup and was open to patients with mesothelioma who were not candidates for surgery and had not received chemotherapy. Those who had pleural effusion were allowed to undergo a talc pleurodesis at the time of diagnostic thoracoscopy.

A total of 448 patients were randomized to open-label cisplatin and pemetrexed, with versus without bevacizumab (Avastin). The bevacizumab group additionally received the drug alone as maintenance therapy after completing chemotherapy. Cross-over was not allowed.

With a median follow-up of 39.4 months, the bevacizumab arm had better median overall survival (18.82 vs. 16.07 months; hazard ratio, 0.76; P = .015)—the trial’s primary endpoint—and progression-free survival (9.59 vs. 7.48 months; hazard ratio, 0.61; P less than .0001).

“Usually the progression-free survival in the trials with best medical treatment was between 6 and 7 months,” Dr. Scherpereel pointed out. Similarly, “the best [overall survival] results with the standard treatment is close to 13 months.”

“There was no significant difference between the two arms in the percentage of drug delivery or the percentage of patients having second-line treatment which could explain the increase of survival in the bevacizumab arm,” he reported.

The proportion of patients experiencing grade 3 or 4 toxicity was higher with bevacizumab (71.2% vs. 62.1%; P = .04), largely because of more nonhematologic toxicity such as hypertension and venous thromboembolism. However, this additional toxicity was manageable, according to Dr. Scherpereel.

Furthermore, in terms of quality of life measures, patients in the bevacizumab arm had a greater improvement in fatigue from baseline (P = .046) and scores for other measures did not differ between arms.

“We did not find some predictive clinical or biological marker [of bevacizumab benefit] for this study,” he said. In particular, patients’ pretreatment levels of vascular endothelial growth factor (VEGF) did not identify a group more likely to benefit. But an ongoing companion study is still evaluating other biomarkers, such as mesothelin and endocan, he added.

Dr. Scherpereel disclosed that he and coinvestigators had affiliations with Roche and other companies. Roche supplied bevacizumab and a research grant for the biomarker studies.

DENVER – Adding the antiangiogenic antibody bevacizumab to chemotherapy improves outcomes in patients who have unresectable mesothelioma, with little downside, according to results of MAPS (the Mesothelioma Avastin Plus Pemetrexed-Cisplatin Study).

Median overall survival in the multicenter randomized phase III trial was 2.75 months longer for patients given bevacizumab in addition to the doublet of pemetrexed plus cisplatin, first author Dr. Arnaud Scherpereel reported at a world conference on lung cancer. This benefit was achieved with only a small increase in the rate of grade 3 or 4 toxicity and no detriment to quality of life.

“We feel that the treatment of pemetrexed-cisplatin with bevacizumab is a new treatment paradigm for mesothelioma patients eligible for bevacizumab and not candidates for curative surgery. And I think that most of them may be eligible for this drug because these patients are not so often smokers and [have] lung conservation, they have less comorbidities,” he said. “Perhaps this treatment may be accepted as a new standard of care for these patients.”

The control arm had much better survival than had been seen historically with this chemotherapy, noted Dr. Scherpereel, who is head of the pulmonary and thoracic oncology department and a professor at the University Hospital (CHRU) of Lille, France. This may have been because of the trial’s eligibility criteria, chosen to ensure that patients could receive bevacizumab, or to the facts that patients had to be fit enough to undergo thoracoscopy and that some received pleurodesis before enrollment.

Bevacizumab benefit may therefore differ in other patients, he acknowledged. “We will see in the real life. I hope first to have the drug [available] for this indication,” he said an the conference sponsored by the International Association for the Study of Lung Cancer.

Press conference moderator Dr. James R. Jett, conference cochair and a professor of medicine at National Jewish Health in Denver, noted that pemetrexed-cisplatin remains the standard of care in the United States. “We don’t have bevacizumab as the standard, but this [trial] may very well change that,” he said.

He wondered if the unusually good outcomes in the control arm were related to earlier diagnosis, but said that regardless, bevacizumab still showed a benefit. “I think the main message here is that it’s important to do concurrent controls because if we were comparing to a historic control, it would be very difficult,” he said.

MAPS was sponsored by the French Cooperative Thoracic Intergroup and was open to patients with mesothelioma who were not candidates for surgery and had not received chemotherapy. Those who had pleural effusion were allowed to undergo a talc pleurodesis at the time of diagnostic thoracoscopy.

A total of 448 patients were randomized to open-label cisplatin and pemetrexed, with versus without bevacizumab (Avastin). The bevacizumab group additionally received the drug alone as maintenance therapy after completing chemotherapy. Cross-over was not allowed.

With a median follow-up of 39.4 months, the bevacizumab arm had better median overall survival (18.82 vs. 16.07 months; hazard ratio, 0.76; P = .015)—the trial’s primary endpoint—and progression-free survival (9.59 vs. 7.48 months; hazard ratio, 0.61; P less than .0001).

“Usually the progression-free survival in the trials with best medical treatment was between 6 and 7 months,” Dr. Scherpereel pointed out. Similarly, “the best [overall survival] results with the standard treatment is close to 13 months.”

“There was no significant difference between the two arms in the percentage of drug delivery or the percentage of patients having second-line treatment which could explain the increase of survival in the bevacizumab arm,” he reported.

The proportion of patients experiencing grade 3 or 4 toxicity was higher with bevacizumab (71.2% vs. 62.1%; P = .04), largely because of more nonhematologic toxicity such as hypertension and venous thromboembolism. However, this additional toxicity was manageable, according to Dr. Scherpereel.

Furthermore, in terms of quality of life measures, patients in the bevacizumab arm had a greater improvement in fatigue from baseline (P = .046) and scores for other measures did not differ between arms.

“We did not find some predictive clinical or biological marker [of bevacizumab benefit] for this study,” he said. In particular, patients’ pretreatment levels of vascular endothelial growth factor (VEGF) did not identify a group more likely to benefit. But an ongoing companion study is still evaluating other biomarkers, such as mesothelin and endocan, he added.

Dr. Scherpereel disclosed that he and coinvestigators had affiliations with Roche and other companies. Roche supplied bevacizumab and a research grant for the biomarker studies.

LONDON – The majority of patients with severe heart failure had sleep-disordered breathing and, in most affected patients, this manifested as obstructive sleep apnea, in an analysis of more than 1,000 German heart failure patients enrolled in a multicenter registry.

“The vast majority of heart failure patients with sleep-disordered breathing [SDB] have obstructive sleep apnea, which differs from previous results,” said Dr. Olaf Oldenburg at the annual congress of the European Society of Cardiology. Possible reasons why this German registry had different findings, compared with prior reports, were its inclusion of heart failure patients with milder symptoms, inclusion of patients with preserved ejection fraction, and inclusion of more women, suggested Dr. Oldenburg, director of the sleep laboratory at the Heart and Diabetes Center of Ruhr University of Bochum in Bad Oeynhausen, Germany.

His finding that nearly two-thirds of the heart failure patients with SDB in this registry had obstructive sleep apnea and that one-third had moderate or severe obstructive sleep apnea was notable because this remains a form of sleep-disordered breathing that can be treated, he said. “There is still enough evidence to treat obstructive sleep apnea” in heart failure patients when it has a moderate or severe presentation, which is defined as causing 15 or more apnea-hypopnea events/hour during sleep. “Obstructive sleep apnea is definitely not a compensatory mechanism in heart failure,” Dr. Oldenburg said.

He highlighted the ongoing need to treat more severe obstructive sleep apnea in heart failure patients because this form of SDB sharply contrasts with the results of the SERVE-HF trial, also reported at the congress, which showed that in patients with advanced heart failure and central sleep apnea nocturnal treatment with adaptive servo ventilation failed to provide benefit and also appeared to boost patient mortality (N Engl J Med. 2015 Sep 17;373[12]:1095-105).

Following that report “we need to think about which heart failure patients to treat” with nocturnal ventilation, and differentiate between heart failure patients with obstructive sleep apnea and those with central sleep apnea, Dr. Oldenburg said.

The data he reported came from the SchlaHF-XT (Sleep Disordered Breathing in Heart Failure) registry, which enrolled patients with heart failure and reduced or preserved ejection fraction and any New York Heart Association functional class treated either at German hospitals or in physician offices. He reported data for 1,186 fully assessed and classified patients, who averaged 68 years old and two-thirds of whom were men. Slightly more than half had heart failure with reduced ejection fraction, and about half had New York Heart Association class II heart failure, a quarter had class III heart failure, with the remaining patients divided roughly equally between class I and IV.

Screening for SDB showed that 24% had no SDB, 37% had mild SBD, 21% had moderate SDB, and 19% had severe SDB (percentages total 101% because of rounding). Among those with SDB, 64% had obstructive sleep apnea, 22% had central sleep apnea, and the remaining 14% had either a mixed form of sleep apnea or were not classifiable.

The analysis also showed that moderate and severe SDB, the forms that require treatment, occurred more often among patients with heart failure and reduced ejection fraction, 43%, compared with patients with heart failure and preserved ejection fraction, who had a 36% prevalence of SDB requiring treatment. Moderate or severe central sleep apnea occurred in 15% of patients with reduced ejection fraction and in 9% of patients with preserved ejection fraction.

A second report at the congress by Dr. Oldenburg showed that the duration of time when a patient’s oxygen saturation fell below 90% was a better gauge of the severity of SDB than was the traditional measure of the apnea-hypopnea index (AHI), the average number of apnea-hypopnea episodes a patient has during an hour of sleep. For this analysis, he used data collected on 963 patients with chronic, stable heart failure with reduced ejection fraction who underwent a comprehensive sleep study with pulse oximetry measurements during 2002-2013.

The results showed that while the measured AHI significantly linked with the 5-year mortality rate of these patients, the relationship became statistically insignificant after researchers adjusted for age, sex, body mass index, heart failure severity, ejection fraction, medications, and other clinical variables.

In contrast, the average time a patient spent with an oxygen saturation level below 90% overnight strong linked with 5-year mortality even after adjusting for all these covariables. The analysis showed that each hour of sleep a heart failure patient spent with an oxygen saturation level below 90% linked with a relative 16% reduction in 5-year survival. Patients in the quartile with the greatest amount of time spent with a oxygen saturation level below 90% had a 50% 5-year mortality rate, while those in the quartile with the least amount of time spent with severely depressed oxygen saturation had a 30% 5-year mortality rate.

Based on this finding “you need to look at the effect of SDB and not just the apnea-hypopnea index” when assessing SDB in patients with heart failure, Dr. Oldenburg said.

[email protected]

On Twitter @mitchelzoler

LONDON – The majority of patients with severe heart failure had sleep-disordered breathing and, in most affected patients, this manifested as obstructive sleep apnea, in an analysis of more than 1,000 German heart failure patients enrolled in a multicenter registry.

“The vast majority of heart failure patients with sleep-disordered breathing [SDB] have obstructive sleep apnea, which differs from previous results,” said Dr. Olaf Oldenburg at the annual congress of the European Society of Cardiology. Possible reasons why this German registry had different findings, compared with prior reports, were its inclusion of heart failure patients with milder symptoms, inclusion of patients with preserved ejection fraction, and inclusion of more women, suggested Dr. Oldenburg, director of the sleep laboratory at the Heart and Diabetes Center of Ruhr University of Bochum in Bad Oeynhausen, Germany.

His finding that nearly two-thirds of the heart failure patients with SDB in this registry had obstructive sleep apnea and that one-third had moderate or severe obstructive sleep apnea was notable because this remains a form of sleep-disordered breathing that can be treated, he said. “There is still enough evidence to treat obstructive sleep apnea” in heart failure patients when it has a moderate or severe presentation, which is defined as causing 15 or more apnea-hypopnea events/hour during sleep. “Obstructive sleep apnea is definitely not a compensatory mechanism in heart failure,” Dr. Oldenburg said.

He highlighted the ongoing need to treat more severe obstructive sleep apnea in heart failure patients because this form of SDB sharply contrasts with the results of the SERVE-HF trial, also reported at the congress, which showed that in patients with advanced heart failure and central sleep apnea nocturnal treatment with adaptive servo ventilation failed to provide benefit and also appeared to boost patient mortality (N Engl J Med. 2015 Sep 17;373[12]:1095-105).

Following that report “we need to think about which heart failure patients to treat” with nocturnal ventilation, and differentiate between heart failure patients with obstructive sleep apnea and those with central sleep apnea, Dr. Oldenburg said.

The data he reported came from the SchlaHF-XT (Sleep Disordered Breathing in Heart Failure) registry, which enrolled patients with heart failure and reduced or preserved ejection fraction and any New York Heart Association functional class treated either at German hospitals or in physician offices. He reported data for 1,186 fully assessed and classified patients, who averaged 68 years old and two-thirds of whom were men. Slightly more than half had heart failure with reduced ejection fraction, and about half had New York Heart Association class II heart failure, a quarter had class III heart failure, with the remaining patients divided roughly equally between class I and IV.

Screening for SDB showed that 24% had no SDB, 37% had mild SBD, 21% had moderate SDB, and 19% had severe SDB (percentages total 101% because of rounding). Among those with SDB, 64% had obstructive sleep apnea, 22% had central sleep apnea, and the remaining 14% had either a mixed form of sleep apnea or were not classifiable.

The analysis also showed that moderate and severe SDB, the forms that require treatment, occurred more often among patients with heart failure and reduced ejection fraction, 43%, compared with patients with heart failure and preserved ejection fraction, who had a 36% prevalence of SDB requiring treatment. Moderate or severe central sleep apnea occurred in 15% of patients with reduced ejection fraction and in 9% of patients with preserved ejection fraction.

A second report at the congress by Dr. Oldenburg showed that the duration of time when a patient’s oxygen saturation fell below 90% was a better gauge of the severity of SDB than was the traditional measure of the apnea-hypopnea index (AHI), the average number of apnea-hypopnea episodes a patient has during an hour of sleep. For this analysis, he used data collected on 963 patients with chronic, stable heart failure with reduced ejection fraction who underwent a comprehensive sleep study with pulse oximetry measurements during 2002-2013.

The results showed that while the measured AHI significantly linked with the 5-year mortality rate of these patients, the relationship became statistically insignificant after researchers adjusted for age, sex, body mass index, heart failure severity, ejection fraction, medications, and other clinical variables.

In contrast, the average time a patient spent with an oxygen saturation level below 90% overnight strong linked with 5-year mortality even after adjusting for all these covariables. The analysis showed that each hour of sleep a heart failure patient spent with an oxygen saturation level below 90% linked with a relative 16% reduction in 5-year survival. Patients in the quartile with the greatest amount of time spent with a oxygen saturation level below 90% had a 50% 5-year mortality rate, while those in the quartile with the least amount of time spent with severely depressed oxygen saturation had a 30% 5-year mortality rate.

Based on this finding “you need to look at the effect of SDB and not just the apnea-hypopnea index” when assessing SDB in patients with heart failure, Dr. Oldenburg said.

[email protected]

On Twitter @mitchelzoler

LONDON – The majority of patients with severe heart failure had sleep-disordered breathing and, in most affected patients, this manifested as obstructive sleep apnea, in an analysis of more than 1,000 German heart failure patients enrolled in a multicenter registry.

“The vast majority of heart failure patients with sleep-disordered breathing [SDB] have obstructive sleep apnea, which differs from previous results,” said Dr. Olaf Oldenburg at the annual congress of the European Society of Cardiology. Possible reasons why this German registry had different findings, compared with prior reports, were its inclusion of heart failure patients with milder symptoms, inclusion of patients with preserved ejection fraction, and inclusion of more women, suggested Dr. Oldenburg, director of the sleep laboratory at the Heart and Diabetes Center of Ruhr University of Bochum in Bad Oeynhausen, Germany.

His finding that nearly two-thirds of the heart failure patients with SDB in this registry had obstructive sleep apnea and that one-third had moderate or severe obstructive sleep apnea was notable because this remains a form of sleep-disordered breathing that can be treated, he said. “There is still enough evidence to treat obstructive sleep apnea” in heart failure patients when it has a moderate or severe presentation, which is defined as causing 15 or more apnea-hypopnea events/hour during sleep. “Obstructive sleep apnea is definitely not a compensatory mechanism in heart failure,” Dr. Oldenburg said.

He highlighted the ongoing need to treat more severe obstructive sleep apnea in heart failure patients because this form of SDB sharply contrasts with the results of the SERVE-HF trial, also reported at the congress, which showed that in patients with advanced heart failure and central sleep apnea nocturnal treatment with adaptive servo ventilation failed to provide benefit and also appeared to boost patient mortality (N Engl J Med. 2015 Sep 17;373[12]:1095-105).

Following that report “we need to think about which heart failure patients to treat” with nocturnal ventilation, and differentiate between heart failure patients with obstructive sleep apnea and those with central sleep apnea, Dr. Oldenburg said.

The data he reported came from the SchlaHF-XT (Sleep Disordered Breathing in Heart Failure) registry, which enrolled patients with heart failure and reduced or preserved ejection fraction and any New York Heart Association functional class treated either at German hospitals or in physician offices. He reported data for 1,186 fully assessed and classified patients, who averaged 68 years old and two-thirds of whom were men. Slightly more than half had heart failure with reduced ejection fraction, and about half had New York Heart Association class II heart failure, a quarter had class III heart failure, with the remaining patients divided roughly equally between class I and IV.

Screening for SDB showed that 24% had no SDB, 37% had mild SBD, 21% had moderate SDB, and 19% had severe SDB (percentages total 101% because of rounding). Among those with SDB, 64% had obstructive sleep apnea, 22% had central sleep apnea, and the remaining 14% had either a mixed form of sleep apnea or were not classifiable.

The analysis also showed that moderate and severe SDB, the forms that require treatment, occurred more often among patients with heart failure and reduced ejection fraction, 43%, compared with patients with heart failure and preserved ejection fraction, who had a 36% prevalence of SDB requiring treatment. Moderate or severe central sleep apnea occurred in 15% of patients with reduced ejection fraction and in 9% of patients with preserved ejection fraction.

A second report at the congress by Dr. Oldenburg showed that the duration of time when a patient’s oxygen saturation fell below 90% was a better gauge of the severity of SDB than was the traditional measure of the apnea-hypopnea index (AHI), the average number of apnea-hypopnea episodes a patient has during an hour of sleep. For this analysis, he used data collected on 963 patients with chronic, stable heart failure with reduced ejection fraction who underwent a comprehensive sleep study with pulse oximetry measurements during 2002-2013.

The results showed that while the measured AHI significantly linked with the 5-year mortality rate of these patients, the relationship became statistically insignificant after researchers adjusted for age, sex, body mass index, heart failure severity, ejection fraction, medications, and other clinical variables.

In contrast, the average time a patient spent with an oxygen saturation level below 90% overnight strong linked with 5-year mortality even after adjusting for all these covariables. The analysis showed that each hour of sleep a heart failure patient spent with an oxygen saturation level below 90% linked with a relative 16% reduction in 5-year survival. Patients in the quartile with the greatest amount of time spent with a oxygen saturation level below 90% had a 50% 5-year mortality rate, while those in the quartile with the least amount of time spent with severely depressed oxygen saturation had a 30% 5-year mortality rate.

Based on this finding “you need to look at the effect of SDB and not just the apnea-hypopnea index” when assessing SDB in patients with heart failure, Dr. Oldenburg said.

[email protected]

On Twitter @mitchelzoler

Half (50.3%) of women who were pregnant at any time from October 2014 through January 2015 received influenza vaccination before or during pregnancy, according to responses from 1,702 participants in an Internet panel survey conducted by the Centers for Disease Control and Prevention.

Vaccination rates for pregnant women during the 2014-15 flu season are similar to rates over the past few years, with 52.2% getting vaccinated in 2013-14 season, 50.5% in 2012-13, and 46.4% in 2011-12. Vaccination coverage, however, was substantially higher when a physician or other health care provider offered the vaccine.

Of the 64.9% of women who received a vaccination offer, 67.9% chose to get the influenza vaccination. Among the 14.8% of survey participants whose health care provider recommended vaccination but didn’t offer it, 33.5% got vaccinated. And of the 20.3% of patients who didn’t receive a recommendation for the influenza vaccination, 8.5% got the vaccine.

©AvailableLight/istockphoto.com

“Even among women who reported negative attitudes regarding influenza vaccine efficacy or safety, or were not concerned about influenza infection, coverage was higher among those whose provider recommended and offered vaccination than among women with the same belief who reported only receiving a provider recommendation or receiving no recommendation,” Dr. Helen Ding and her colleagues wrote in the CDC’s Morbidity and Mortality Weekly Report (2015 Sept. 18;64[36];1000-5.).

Negative attitudes about safety and efficacy were the most common reasons that study participants rejected the flu vaccination, with 17.2% saying that they didn’t think the vaccination was effective, 14.5% saying that they were worried about the possible safety risks to their baby, and 13.6% expressing concern that the vaccination would give them the flu.

“Efforts are needed to improve influenza vaccination coverage among pregnant women. Interventions should include implementing clinic-based education to ensure access to information about influenza vaccine safety and efficacy and the risk for influenza for pregnant women and their infants, and systems to ensure that providers recommend and offer influenza vaccination to all pregnant women,” the researchers wrote.

Read the full article in MMWR.

[email protected]

Half (50.3%) of women who were pregnant at any time from October 2014 through January 2015 received influenza vaccination before or during pregnancy, according to responses from 1,702 participants in an Internet panel survey conducted by the Centers for Disease Control and Prevention.

Vaccination rates for pregnant women during the 2014-15 flu season are similar to rates over the past few years, with 52.2% getting vaccinated in 2013-14 season, 50.5% in 2012-13, and 46.4% in 2011-12. Vaccination coverage, however, was substantially higher when a physician or other health care provider offered the vaccine.

Of the 64.9% of women who received a vaccination offer, 67.9% chose to get the influenza vaccination. Among the 14.8% of survey participants whose health care provider recommended vaccination but didn’t offer it, 33.5% got vaccinated. And of the 20.3% of patients who didn’t receive a recommendation for the influenza vaccination, 8.5% got the vaccine.

©AvailableLight/istockphoto.com

“Even among women who reported negative attitudes regarding influenza vaccine efficacy or safety, or were not concerned about influenza infection, coverage was higher among those whose provider recommended and offered vaccination than among women with the same belief who reported only receiving a provider recommendation or receiving no recommendation,” Dr. Helen Ding and her colleagues wrote in the CDC’s Morbidity and Mortality Weekly Report (2015 Sept. 18;64[36];1000-5.).

Negative attitudes about safety and efficacy were the most common reasons that study participants rejected the flu vaccination, with 17.2% saying that they didn’t think the vaccination was effective, 14.5% saying that they were worried about the possible safety risks to their baby, and 13.6% expressing concern that the vaccination would give them the flu.

“Efforts are needed to improve influenza vaccination coverage among pregnant women. Interventions should include implementing clinic-based education to ensure access to information about influenza vaccine safety and efficacy and the risk for influenza for pregnant women and their infants, and systems to ensure that providers recommend and offer influenza vaccination to all pregnant women,” the researchers wrote.

Read the full article in MMWR.

[email protected]

Half (50.3%) of women who were pregnant at any time from October 2014 through January 2015 received influenza vaccination before or during pregnancy, according to responses from 1,702 participants in an Internet panel survey conducted by the Centers for Disease Control and Prevention.

Vaccination rates for pregnant women during the 2014-15 flu season are similar to rates over the past few years, with 52.2% getting vaccinated in 2013-14 season, 50.5% in 2012-13, and 46.4% in 2011-12. Vaccination coverage, however, was substantially higher when a physician or other health care provider offered the vaccine.

Of the 64.9% of women who received a vaccination offer, 67.9% chose to get the influenza vaccination. Among the 14.8% of survey participants whose health care provider recommended vaccination but didn’t offer it, 33.5% got vaccinated. And of the 20.3% of patients who didn’t receive a recommendation for the influenza vaccination, 8.5% got the vaccine.

©AvailableLight/istockphoto.com

“Even among women who reported negative attitudes regarding influenza vaccine efficacy or safety, or were not concerned about influenza infection, coverage was higher among those whose provider recommended and offered vaccination than among women with the same belief who reported only receiving a provider recommendation or receiving no recommendation,” Dr. Helen Ding and her colleagues wrote in the CDC’s Morbidity and Mortality Weekly Report (2015 Sept. 18;64[36];1000-5.).

Negative attitudes about safety and efficacy were the most common reasons that study participants rejected the flu vaccination, with 17.2% saying that they didn’t think the vaccination was effective, 14.5% saying that they were worried about the possible safety risks to their baby, and 13.6% expressing concern that the vaccination would give them the flu.

“Efforts are needed to improve influenza vaccination coverage among pregnant women. Interventions should include implementing clinic-based education to ensure access to information about influenza vaccine safety and efficacy and the risk for influenza for pregnant women and their infants, and systems to ensure that providers recommend and offer influenza vaccination to all pregnant women,” the researchers wrote.

Read the full article in MMWR.

[email protected]

A double espresso-sized dose of caffeine consumed 3 hours before bedtime delayed the normal onset of the melatonin rhythm by about 40 minutes, researchers reported in Science Translational Medicine.

“In addition to increasing daytime exposure to sunlight and reducing evening exposure to electrical light, avoiding evening caffeine may help treat problematic delayed sleep timing,” according to Tina Burke of the University of Colorado Boulder and her associates. The results also could support consuming caffeine in the morning to help recover from jet lag, but further studies would need to test that possibility, the researchers added.

SorJongAng/Thinkstock.com

Caffeine is known to affect circadian rhythms in rats and flies, but its circadian effects in humans were unknown, said the investigators. Their 49-day, double-blinded study included five healthy, normal-weight adults who averaged 24 years of age. For a week before each scheduled laboratory visit, participants slept 8 hours a night as verified with the help of sleep logs, wrist actigraphy, and time-stamped voice mail reminders. In the laboratory, they received caffeine or placebo 3 hours before their normal bedtime and were exposed to either bright or dim (control) light at bedtime (Sci Transl Med. 2015;7:1-9).

Caffeine plus dim light was associated with about a 40-minute longer phase delay than placebo and dim light (P = .011), the investigators reported. Bright light with placebo led to about a 85-minute phase delay (P = .0007), while bright light plus caffeine caused a 105-minute shift (P = .0003). Experiments with cultured human cells also showed that caffeine competitively bound to adenosine receptors, which disrupted signaling of cyclic adenosine monophosphate (cAMP), a key part of the circadian clock, the researchers said.

The study was funded by the National Institutes of Health, the National Center for Advancing Translational Sciences, and the Howard Hughes Medical Institute in collaboration with the University of Colorado. Ms. Burke declared no competing interests.

A double espresso-sized dose of caffeine consumed 3 hours before bedtime delayed the normal onset of the melatonin rhythm by about 40 minutes, researchers reported in Science Translational Medicine.

“In addition to increasing daytime exposure to sunlight and reducing evening exposure to electrical light, avoiding evening caffeine may help treat problematic delayed sleep timing,” according to Tina Burke of the University of Colorado Boulder and her associates. The results also could support consuming caffeine in the morning to help recover from jet lag, but further studies would need to test that possibility, the researchers added.

SorJongAng/Thinkstock.com

Caffeine is known to affect circadian rhythms in rats and flies, but its circadian effects in humans were unknown, said the investigators. Their 49-day, double-blinded study included five healthy, normal-weight adults who averaged 24 years of age. For a week before each scheduled laboratory visit, participants slept 8 hours a night as verified with the help of sleep logs, wrist actigraphy, and time-stamped voice mail reminders. In the laboratory, they received caffeine or placebo 3 hours before their normal bedtime and were exposed to either bright or dim (control) light at bedtime (Sci Transl Med. 2015;7:1-9).

Caffeine plus dim light was associated with about a 40-minute longer phase delay than placebo and dim light (P = .011), the investigators reported. Bright light with placebo led to about a 85-minute phase delay (P = .0007), while bright light plus caffeine caused a 105-minute shift (P = .0003). Experiments with cultured human cells also showed that caffeine competitively bound to adenosine receptors, which disrupted signaling of cyclic adenosine monophosphate (cAMP), a key part of the circadian clock, the researchers said.

The study was funded by the National Institutes of Health, the National Center for Advancing Translational Sciences, and the Howard Hughes Medical Institute in collaboration with the University of Colorado. Ms. Burke declared no competing interests.

A double espresso-sized dose of caffeine consumed 3 hours before bedtime delayed the normal onset of the melatonin rhythm by about 40 minutes, researchers reported in Science Translational Medicine.

“In addition to increasing daytime exposure to sunlight and reducing evening exposure to electrical light, avoiding evening caffeine may help treat problematic delayed sleep timing,” according to Tina Burke of the University of Colorado Boulder and her associates. The results also could support consuming caffeine in the morning to help recover from jet lag, but further studies would need to test that possibility, the researchers added.

SorJongAng/Thinkstock.com

Caffeine is known to affect circadian rhythms in rats and flies, but its circadian effects in humans were unknown, said the investigators. Their 49-day, double-blinded study included five healthy, normal-weight adults who averaged 24 years of age. For a week before each scheduled laboratory visit, participants slept 8 hours a night as verified with the help of sleep logs, wrist actigraphy, and time-stamped voice mail reminders. In the laboratory, they received caffeine or placebo 3 hours before their normal bedtime and were exposed to either bright or dim (control) light at bedtime (Sci Transl Med. 2015;7:1-9).

Caffeine plus dim light was associated with about a 40-minute longer phase delay than placebo and dim light (P = .011), the investigators reported. Bright light with placebo led to about a 85-minute phase delay (P = .0007), while bright light plus caffeine caused a 105-minute shift (P = .0003). Experiments with cultured human cells also showed that caffeine competitively bound to adenosine receptors, which disrupted signaling of cyclic adenosine monophosphate (cAMP), a key part of the circadian clock, the researchers said.

The study was funded by the National Institutes of Health, the National Center for Advancing Translational Sciences, and the Howard Hughes Medical Institute in collaboration with the University of Colorado. Ms. Burke declared no competing interests.

More than one-tenth of Americans were current users of illicit drugs in 2014, and drug use among adults – marijuana in particular – was on the rise.

An estimated 27 million people, or 10.2% of Americans, used an illicit drug within the previous month, according to the 2014 National Survey on Drug Use and Health (NSDUH), released Sept. 10 by the Substance Abuse and Mental Health Services Administration (SAMHSA).

©Thinkstock.com

About 22 million of those people used marijuana within the previous month, and 4.3 million took prescription pain relievers for nonmedical purposes.

Some 8.4% of Americans aged 12 and older reported current marijuana use, an increase from previous survey years, and 1.6% reported current nonmedical use of pain drugs, a trend that has remained fairly steady, according to the survey.

A significant uptick in nonmedical use of marijuana was seen among adults aged 26 and older, Kana Enomoto, SAMHSA’s acting administrator, said at a Sept. 10 news conference.

Some 6.6% of these adults, or about 13.5 million people, reported being users of marijuana last year, compared with 5.6% in 2013 (P less than .5). Steady increases in marijuana use in this age group have been noted for about a decade.

Heroin use also was higher than in previous years, with an estimated 435,000 users in the United States in 2014, a statistically significant jump from 0.1% of the population aged 12 and older in 2013 to 0.2% last year, with most of the increase driven by people 26 and older.

An estimated 1.5 million Americans, or 0.6% of the population aged 12 and older, were current users of cocaine, including some 354,000 current users of crack cocaine. Cocaine use was similar to patterns seen in recent years.

Overall, current illicit drug use trends appeared to be holding steady or declining in younger age groups, but the increases in adult use are “concerning,” particularly for heroin, said Ms. Enomoto.

Recent declines in alcohol and tobacco use among young people appeared to be holding up. Among adolescents aged 12-17, 4.9% had smoked cigarettes in the previous month, down from 5.6% in 2013 and 6.6% in 2012.

Alcohol use and use patterns among young people were little changed from 2013, and overall incidence of substance use disorders hovered at 8.1% for 2014 among people 12 and older.

The incidence of mental health disorders, including any mental illness and serious mental illness (18.1% and 4.1% of adults over 18, respectively), remained little changed from recent years. Co-occurring mental illness and substance use disorders were at 3.3% of all adults, similar to rates seen since 2006.

The NSDUH data were collected through face-to-face interviews with nearly 68,000 Americans in 2014.

More than one-tenth of Americans were current users of illicit drugs in 2014, and drug use among adults – marijuana in particular – was on the rise.

An estimated 27 million people, or 10.2% of Americans, used an illicit drug within the previous month, according to the 2014 National Survey on Drug Use and Health (NSDUH), released Sept. 10 by the Substance Abuse and Mental Health Services Administration (SAMHSA).

©Thinkstock.com

About 22 million of those people used marijuana within the previous month, and 4.3 million took prescription pain relievers for nonmedical purposes.

Some 8.4% of Americans aged 12 and older reported current marijuana use, an increase from previous survey years, and 1.6% reported current nonmedical use of pain drugs, a trend that has remained fairly steady, according to the survey.

A significant uptick in nonmedical use of marijuana was seen among adults aged 26 and older, Kana Enomoto, SAMHSA’s acting administrator, said at a Sept. 10 news conference.

Some 6.6% of these adults, or about 13.5 million people, reported being users of marijuana last year, compared with 5.6% in 2013 (P less than .5). Steady increases in marijuana use in this age group have been noted for about a decade.

Heroin use also was higher than in previous years, with an estimated 435,000 users in the United States in 2014, a statistically significant jump from 0.1% of the population aged 12 and older in 2013 to 0.2% last year, with most of the increase driven by people 26 and older.

An estimated 1.5 million Americans, or 0.6% of the population aged 12 and older, were current users of cocaine, including some 354,000 current users of crack cocaine. Cocaine use was similar to patterns seen in recent years.

Overall, current illicit drug use trends appeared to be holding steady or declining in younger age groups, but the increases in adult use are “concerning,” particularly for heroin, said Ms. Enomoto.

Recent declines in alcohol and tobacco use among young people appeared to be holding up. Among adolescents aged 12-17, 4.9% had smoked cigarettes in the previous month, down from 5.6% in 2013 and 6.6% in 2012.

Alcohol use and use patterns among young people were little changed from 2013, and overall incidence of substance use disorders hovered at 8.1% for 2014 among people 12 and older.

The incidence of mental health disorders, including any mental illness and serious mental illness (18.1% and 4.1% of adults over 18, respectively), remained little changed from recent years. Co-occurring mental illness and substance use disorders were at 3.3% of all adults, similar to rates seen since 2006.

The NSDUH data were collected through face-to-face interviews with nearly 68,000 Americans in 2014.

More than one-tenth of Americans were current users of illicit drugs in 2014, and drug use among adults – marijuana in particular – was on the rise.

An estimated 27 million people, or 10.2% of Americans, used an illicit drug within the previous month, according to the 2014 National Survey on Drug Use and Health (NSDUH), released Sept. 10 by the Substance Abuse and Mental Health Services Administration (SAMHSA).

©Thinkstock.com

About 22 million of those people used marijuana within the previous month, and 4.3 million took prescription pain relievers for nonmedical purposes.

Some 8.4% of Americans aged 12 and older reported current marijuana use, an increase from previous survey years, and 1.6% reported current nonmedical use of pain drugs, a trend that has remained fairly steady, according to the survey.

A significant uptick in nonmedical use of marijuana was seen among adults aged 26 and older, Kana Enomoto, SAMHSA’s acting administrator, said at a Sept. 10 news conference.

Some 6.6% of these adults, or about 13.5 million people, reported being users of marijuana last year, compared with 5.6% in 2013 (P less than .5). Steady increases in marijuana use in this age group have been noted for about a decade.

Heroin use also was higher than in previous years, with an estimated 435,000 users in the United States in 2014, a statistically significant jump from 0.1% of the population aged 12 and older in 2013 to 0.2% last year, with most of the increase driven by people 26 and older.

An estimated 1.5 million Americans, or 0.6% of the population aged 12 and older, were current users of cocaine, including some 354,000 current users of crack cocaine. Cocaine use was similar to patterns seen in recent years.

Overall, current illicit drug use trends appeared to be holding steady or declining in younger age groups, but the increases in adult use are “concerning,” particularly for heroin, said Ms. Enomoto.

Recent declines in alcohol and tobacco use among young people appeared to be holding up. Among adolescents aged 12-17, 4.9% had smoked cigarettes in the previous month, down from 5.6% in 2013 and 6.6% in 2012.

Alcohol use and use patterns among young people were little changed from 2013, and overall incidence of substance use disorders hovered at 8.1% for 2014 among people 12 and older.

The incidence of mental health disorders, including any mental illness and serious mental illness (18.1% and 4.1% of adults over 18, respectively), remained little changed from recent years. Co-occurring mental illness and substance use disorders were at 3.3% of all adults, similar to rates seen since 2006.

The NSDUH data were collected through face-to-face interviews with nearly 68,000 Americans in 2014.

Lower quality of care was not associated with pneumonia readmissions, according to a study using a commercially available software program to examine possibly preventable readmissions.

Rates of hospital readmission are now being used to demonstrate hospital performance and the Centers for Medicare & Medicaid Services may even penalize hospitals with high rates of readmissions. As a result, it has become increasingly important to recognize clinical situations that may lead to a potentially preventable readmission.

The Potentially Preventable Readmission (PPRs) software was developed by 3M Health Information Systems to identify such cases and is being adopted by some state Medicaid programs for hospital payment and reporting. Dr. Ann M. Borzecki of the Center for Healthcare Organization and Implementation Research in Bedford, Mass., and her colleagues sought to understand if patients with pneumonia flagged by the PPR software as preventable readmissions were associated with failures in the process of care.

The investigators conducted a cross-sectional retrospective observational study with Veterans Affairs electronic medical record (EMR) data from October 2005 to September 2010. Patients with diagnoses of pneumonia and a 30-day readmission were identified and then flagged as PPR-yes (for example, readmissions associated with quality of care problems) vs. PPR-no, using the 3M PPR software. A tool to measure quality of care was applied to 100 random readmissions abstracted for full review. The study was published online Sept. 14 in BMJ Quality and Safety. (http://qualitysafety.bmj.com/lookup/doi/10.1136/bmjqs-2015-003911).

Of all the pneumonia readmission cases, 72% were PPR-yes vs.77% of the 100 abstracted cases. There were no significant differences between the groups other than a trend toward more comorbidity in the PPR-yes group.

Geo Martinez/Thinkstock

After researchers adjusted for comorbidities and demographics, they noted no significant difference in quality of care between the PPR-yes and PPR-no groups. Interestingly, the PPR-yes group had slightly higher quality scores than did the PPR-no group (total scores, 71.2 vs. 65.8 respectively, P = .14).

The authors write, “Among veterans readmitted after a pneumonia discharge, we found no significant difference in quality of care, as measured by processes of care received during the index admission and after discharge, between cases flagged as PPRs and nonflagged cases. Indeed, contrary to our hypothesis, quality scores were slightly higher among PPR-flagged cases.”

The authors emphasized that causes of readmissions are multifaceted and many aspects may be out of the control of the hospital. However, they noted a concern for a lack of postdischarge documentation and emphasized the need for thorough documentation at all levels of care.

The authors report no competing interest. The study was funded by the U.S. Department of Veterans Affairs Health Service Research and Development Service.

Lower quality of care was not associated with pneumonia readmissions, according to a study using a commercially available software program to examine possibly preventable readmissions.

Rates of hospital readmission are now being used to demonstrate hospital performance and the Centers for Medicare & Medicaid Services may even penalize hospitals with high rates of readmissions. As a result, it has become increasingly important to recognize clinical situations that may lead to a potentially preventable readmission.

The Potentially Preventable Readmission (PPRs) software was developed by 3M Health Information Systems to identify such cases and is being adopted by some state Medicaid programs for hospital payment and reporting. Dr. Ann M. Borzecki of the Center for Healthcare Organization and Implementation Research in Bedford, Mass., and her colleagues sought to understand if patients with pneumonia flagged by the PPR software as preventable readmissions were associated with failures in the process of care.

The investigators conducted a cross-sectional retrospective observational study with Veterans Affairs electronic medical record (EMR) data from October 2005 to September 2010. Patients with diagnoses of pneumonia and a 30-day readmission were identified and then flagged as PPR-yes (for example, readmissions associated with quality of care problems) vs. PPR-no, using the 3M PPR software. A tool to measure quality of care was applied to 100 random readmissions abstracted for full review. The study was published online Sept. 14 in BMJ Quality and Safety. (http://qualitysafety.bmj.com/lookup/doi/10.1136/bmjqs-2015-003911).

Of all the pneumonia readmission cases, 72% were PPR-yes vs.77% of the 100 abstracted cases. There were no significant differences between the groups other than a trend toward more comorbidity in the PPR-yes group.

Geo Martinez/Thinkstock

After researchers adjusted for comorbidities and demographics, they noted no significant difference in quality of care between the PPR-yes and PPR-no groups. Interestingly, the PPR-yes group had slightly higher quality scores than did the PPR-no group (total scores, 71.2 vs. 65.8 respectively, P = .14).

The authors write, “Among veterans readmitted after a pneumonia discharge, we found no significant difference in quality of care, as measured by processes of care received during the index admission and after discharge, between cases flagged as PPRs and nonflagged cases. Indeed, contrary to our hypothesis, quality scores were slightly higher among PPR-flagged cases.”

The authors emphasized that causes of readmissions are multifaceted and many aspects may be out of the control of the hospital. However, they noted a concern for a lack of postdischarge documentation and emphasized the need for thorough documentation at all levels of care.

The authors report no competing interest. The study was funded by the U.S. Department of Veterans Affairs Health Service Research and Development Service.

Lower quality of care was not associated with pneumonia readmissions, according to a study using a commercially available software program to examine possibly preventable readmissions.

Rates of hospital readmission are now being used to demonstrate hospital performance and the Centers for Medicare & Medicaid Services may even penalize hospitals with high rates of readmissions. As a result, it has become increasingly important to recognize clinical situations that may lead to a potentially preventable readmission.

The Potentially Preventable Readmission (PPRs) software was developed by 3M Health Information Systems to identify such cases and is being adopted by some state Medicaid programs for hospital payment and reporting. Dr. Ann M. Borzecki of the Center for Healthcare Organization and Implementation Research in Bedford, Mass., and her colleagues sought to understand if patients with pneumonia flagged by the PPR software as preventable readmissions were associated with failures in the process of care.

The investigators conducted a cross-sectional retrospective observational study with Veterans Affairs electronic medical record (EMR) data from October 2005 to September 2010. Patients with diagnoses of pneumonia and a 30-day readmission were identified and then flagged as PPR-yes (for example, readmissions associated with quality of care problems) vs. PPR-no, using the 3M PPR software. A tool to measure quality of care was applied to 100 random readmissions abstracted for full review. The study was published online Sept. 14 in BMJ Quality and Safety. (http://qualitysafety.bmj.com/lookup/doi/10.1136/bmjqs-2015-003911).

Of all the pneumonia readmission cases, 72% were PPR-yes vs.77% of the 100 abstracted cases. There were no significant differences between the groups other than a trend toward more comorbidity in the PPR-yes group.

Geo Martinez/Thinkstock

After researchers adjusted for comorbidities and demographics, they noted no significant difference in quality of care between the PPR-yes and PPR-no groups. Interestingly, the PPR-yes group had slightly higher quality scores than did the PPR-no group (total scores, 71.2 vs. 65.8 respectively, P = .14).

The authors write, “Among veterans readmitted after a pneumonia discharge, we found no significant difference in quality of care, as measured by processes of care received during the index admission and after discharge, between cases flagged as PPRs and nonflagged cases. Indeed, contrary to our hypothesis, quality scores were slightly higher among PPR-flagged cases.”

The authors emphasized that causes of readmissions are multifaceted and many aspects may be out of the control of the hospital. However, they noted a concern for a lack of postdischarge documentation and emphasized the need for thorough documentation at all levels of care.

The authors report no competing interest. The study was funded by the U.S. Department of Veterans Affairs Health Service Research and Development Service.