Pulmonary Health Hub

Tasimelteon, a melatonin-receptor agonist available in the United States, is getting closer to becoming available in the European Union to help regulate sleep patterns in blind people.

On April 24, the European Medicines Agency (EMA) announced that the Committee for Medicinal Products for Human Use (CHMP) had recommended granting authorization for marketing of the drug in the European Union for non-24-hour sleep-wake disorder in “totally blind” adults. Once marketed, this would be the first treatment in Europe for this indication, which the statement describes as a rare and “long-term debilitating condition.”

The drug was shown to be effective in two clinical trials, the results of which showed that treatment resulted in significant improvement, compared with placebo, “both in increasing night-time sleep and decreasing daytime sleep duration,” according to the statement. Headache, drowsiness, and nightmares or “unusual dreams” were among the most common adverse effects associated with treatment.

Tasimelteon was approved in the United States in January 2014 for treating non-24-hour sleep-wake disorder, referred to as “non-24,” at a dose of 20 mg taken before bedtime at the same time every night.

“The precise mechanism by which tasimelteon exerts its therapeutic effect” in patients with non-24 is not known, according to the U.S. prescribing information, which adds that the drug is an agonist at melatonin MT₁ and MT₂ receptors, which are thought to be involved in the control of circadian rhythms.

The trade name used in the EMA release is Hetlioz, the trade name used in the United States.

The EMA is similar to the FDA and the EMA’s CHMP committee prepares opinions on questions related to medications used to treat humans.

The CHMP opinion, adopted at a meeting in April, will be sent to the European Commission for a decision on marketing authorization in the EU. After authorization for marketing has been granted, the decision about cost and reimbursement “will then take place at the level of each Member State considering the potential role/use of this medicine in the context of the national health system of that country,” the EMA release stated.

The drug is manufactured by Vanda Pharmaceuticals.

[email protected]

Tasimelteon, a melatonin-receptor agonist available in the United States, is getting closer to becoming available in the European Union to help regulate sleep patterns in blind people.

On April 24, the European Medicines Agency (EMA) announced that the Committee for Medicinal Products for Human Use (CHMP) had recommended granting authorization for marketing of the drug in the European Union for non-24-hour sleep-wake disorder in “totally blind” adults. Once marketed, this would be the first treatment in Europe for this indication, which the statement describes as a rare and “long-term debilitating condition.”

The drug was shown to be effective in two clinical trials, the results of which showed that treatment resulted in significant improvement, compared with placebo, “both in increasing night-time sleep and decreasing daytime sleep duration,” according to the statement. Headache, drowsiness, and nightmares or “unusual dreams” were among the most common adverse effects associated with treatment.

Tasimelteon was approved in the United States in January 2014 for treating non-24-hour sleep-wake disorder, referred to as “non-24,” at a dose of 20 mg taken before bedtime at the same time every night.

“The precise mechanism by which tasimelteon exerts its therapeutic effect” in patients with non-24 is not known, according to the U.S. prescribing information, which adds that the drug is an agonist at melatonin MT₁ and MT₂ receptors, which are thought to be involved in the control of circadian rhythms.

The trade name used in the EMA release is Hetlioz, the trade name used in the United States.

The EMA is similar to the FDA and the EMA’s CHMP committee prepares opinions on questions related to medications used to treat humans.

The CHMP opinion, adopted at a meeting in April, will be sent to the European Commission for a decision on marketing authorization in the EU. After authorization for marketing has been granted, the decision about cost and reimbursement “will then take place at the level of each Member State considering the potential role/use of this medicine in the context of the national health system of that country,” the EMA release stated.

The drug is manufactured by Vanda Pharmaceuticals.

[email protected]

Tasimelteon, a melatonin-receptor agonist available in the United States, is getting closer to becoming available in the European Union to help regulate sleep patterns in blind people.

On April 24, the European Medicines Agency (EMA) announced that the Committee for Medicinal Products for Human Use (CHMP) had recommended granting authorization for marketing of the drug in the European Union for non-24-hour sleep-wake disorder in “totally blind” adults. Once marketed, this would be the first treatment in Europe for this indication, which the statement describes as a rare and “long-term debilitating condition.”

The drug was shown to be effective in two clinical trials, the results of which showed that treatment resulted in significant improvement, compared with placebo, “both in increasing night-time sleep and decreasing daytime sleep duration,” according to the statement. Headache, drowsiness, and nightmares or “unusual dreams” were among the most common adverse effects associated with treatment.

Tasimelteon was approved in the United States in January 2014 for treating non-24-hour sleep-wake disorder, referred to as “non-24,” at a dose of 20 mg taken before bedtime at the same time every night.

“The precise mechanism by which tasimelteon exerts its therapeutic effect” in patients with non-24 is not known, according to the U.S. prescribing information, which adds that the drug is an agonist at melatonin MT₁ and MT₂ receptors, which are thought to be involved in the control of circadian rhythms.

The trade name used in the EMA release is Hetlioz, the trade name used in the United States.

The EMA is similar to the FDA and the EMA’s CHMP committee prepares opinions on questions related to medications used to treat humans.

The CHMP opinion, adopted at a meeting in April, will be sent to the European Commission for a decision on marketing authorization in the EU. After authorization for marketing has been granted, the decision about cost and reimbursement “will then take place at the level of each Member State considering the potential role/use of this medicine in the context of the national health system of that country,” the EMA release stated.

The drug is manufactured by Vanda Pharmaceuticals.

[email protected]

SAN DIEGO – Implementation of guidelines for the use of the high-flow nasal cannula in general pediatric wards for infants admitted with bronchiolitis can lead to significant decreases in length of stay, need for ICU level of care, and overall hospitalization costs, a retrospective chart study showed.

In the nonrandomized, pre- and postintervention chart analysis, the investigators reviewed the data for 2,446 infants under the age of 2 years who were admitted to Hasbro Children’s Hospital with a diagnosis for bronchiolitis in the 24 months before and after March 2012, when the hospital initiated high-flow nasal cannula (HFNC) protocols in its general pediatric wards.

“Admissions for bronchiolitis are extremely common for children under the age of 1 [year], and the costs associated with this are obviously quite high, but although centers around the country are now using [HFNC] for bronchiolitis, there’s little data at this point regarding the use of it on the general wards,” said Dr. Jamie Fierce of Hasbro Children’s Hospital in Providence, R.I., adding that the 2014 American Academy of Pediatrics guidelines on bronchiolitis called for more research on the efficacy of HFNC (Pediatrics 2014;134:e1474-502).

In total, 533 infants were selected for inclusion in the study, and were divided into groups based on whether they were admitted and discharged before or after the March 2012 implementation of HFNC protocols. The primary outcome measured for the study was the length of hospital stay; the median length before implementation was 4 days, while after implementation, the median length of stay decreased to 3 days (P < .001). In addition, the number of patients who required an ICU level of care decreased from the mandated 100% – because every subject who received HFNC would have to be admitted to the ICU before the new protocols were in place – to 70% of subjects after the new protocols were put in place (P < .001).

The cost of hospitalization also decreased significantly; prior to HFNC use on general wards, the median cost per patient was $12,865, but that amount decreased to $8,952 after March 2012, a difference of almost $4,000. Furthermore, there was no increase in intubation rates, nor in 30-day readmission rates from before to after March 2012. The average number of days spent on HFNC dropped from 2.5 days to 2 days, and the mean maximum HFNC rate also decreased from 9 L/min to 7 L/min, Dr. Fierce reported at the annual meeting of the Pediatric Academic Societies.

“One important limitation to this study is that it’s difficult to assess bronchiolitis severity in each of our groups, so there could have been seasonal variations that may have affected our outcomes,” he said. “Our after-implementation group is larger than our before-implementation group, and it’s hard to tell if that’s due to a seasonal increase in bronchiolitis cases, or if there was just higher use of HFNC on patients once it was allowed in the general wards.”

Demographic information was collected from the hospital billing database on subjects’ age, race, sex, and secondhand smoke exposure and whether they had public or private insurance. Although there was a statistically significant difference in age between the groups – 3 months before March 2012, 5 months after – the other demographic data were largely consistent from before implementation to after.

Dr. Fierce did not report any relevant financial disclosures.

[email protected]

SAN DIEGO – Implementation of guidelines for the use of the high-flow nasal cannula in general pediatric wards for infants admitted with bronchiolitis can lead to significant decreases in length of stay, need for ICU level of care, and overall hospitalization costs, a retrospective chart study showed.

In the nonrandomized, pre- and postintervention chart analysis, the investigators reviewed the data for 2,446 infants under the age of 2 years who were admitted to Hasbro Children’s Hospital with a diagnosis for bronchiolitis in the 24 months before and after March 2012, when the hospital initiated high-flow nasal cannula (HFNC) protocols in its general pediatric wards.

“Admissions for bronchiolitis are extremely common for children under the age of 1 [year], and the costs associated with this are obviously quite high, but although centers around the country are now using [HFNC] for bronchiolitis, there’s little data at this point regarding the use of it on the general wards,” said Dr. Jamie Fierce of Hasbro Children’s Hospital in Providence, R.I., adding that the 2014 American Academy of Pediatrics guidelines on bronchiolitis called for more research on the efficacy of HFNC (Pediatrics 2014;134:e1474-502).

In total, 533 infants were selected for inclusion in the study, and were divided into groups based on whether they were admitted and discharged before or after the March 2012 implementation of HFNC protocols. The primary outcome measured for the study was the length of hospital stay; the median length before implementation was 4 days, while after implementation, the median length of stay decreased to 3 days (P < .001). In addition, the number of patients who required an ICU level of care decreased from the mandated 100% – because every subject who received HFNC would have to be admitted to the ICU before the new protocols were in place – to 70% of subjects after the new protocols were put in place (P < .001).

The cost of hospitalization also decreased significantly; prior to HFNC use on general wards, the median cost per patient was $12,865, but that amount decreased to $8,952 after March 2012, a difference of almost $4,000. Furthermore, there was no increase in intubation rates, nor in 30-day readmission rates from before to after March 2012. The average number of days spent on HFNC dropped from 2.5 days to 2 days, and the mean maximum HFNC rate also decreased from 9 L/min to 7 L/min, Dr. Fierce reported at the annual meeting of the Pediatric Academic Societies.

“One important limitation to this study is that it’s difficult to assess bronchiolitis severity in each of our groups, so there could have been seasonal variations that may have affected our outcomes,” he said. “Our after-implementation group is larger than our before-implementation group, and it’s hard to tell if that’s due to a seasonal increase in bronchiolitis cases, or if there was just higher use of HFNC on patients once it was allowed in the general wards.”

Demographic information was collected from the hospital billing database on subjects’ age, race, sex, and secondhand smoke exposure and whether they had public or private insurance. Although there was a statistically significant difference in age between the groups – 3 months before March 2012, 5 months after – the other demographic data were largely consistent from before implementation to after.

Dr. Fierce did not report any relevant financial disclosures.

[email protected]

SAN DIEGO – Implementation of guidelines for the use of the high-flow nasal cannula in general pediatric wards for infants admitted with bronchiolitis can lead to significant decreases in length of stay, need for ICU level of care, and overall hospitalization costs, a retrospective chart study showed.

In the nonrandomized, pre- and postintervention chart analysis, the investigators reviewed the data for 2,446 infants under the age of 2 years who were admitted to Hasbro Children’s Hospital with a diagnosis for bronchiolitis in the 24 months before and after March 2012, when the hospital initiated high-flow nasal cannula (HFNC) protocols in its general pediatric wards.

“Admissions for bronchiolitis are extremely common for children under the age of 1 [year], and the costs associated with this are obviously quite high, but although centers around the country are now using [HFNC] for bronchiolitis, there’s little data at this point regarding the use of it on the general wards,” said Dr. Jamie Fierce of Hasbro Children’s Hospital in Providence, R.I., adding that the 2014 American Academy of Pediatrics guidelines on bronchiolitis called for more research on the efficacy of HFNC (Pediatrics 2014;134:e1474-502).

In total, 533 infants were selected for inclusion in the study, and were divided into groups based on whether they were admitted and discharged before or after the March 2012 implementation of HFNC protocols. The primary outcome measured for the study was the length of hospital stay; the median length before implementation was 4 days, while after implementation, the median length of stay decreased to 3 days (P < .001). In addition, the number of patients who required an ICU level of care decreased from the mandated 100% – because every subject who received HFNC would have to be admitted to the ICU before the new protocols were in place – to 70% of subjects after the new protocols were put in place (P < .001).

The cost of hospitalization also decreased significantly; prior to HFNC use on general wards, the median cost per patient was $12,865, but that amount decreased to $8,952 after March 2012, a difference of almost $4,000. Furthermore, there was no increase in intubation rates, nor in 30-day readmission rates from before to after March 2012. The average number of days spent on HFNC dropped from 2.5 days to 2 days, and the mean maximum HFNC rate also decreased from 9 L/min to 7 L/min, Dr. Fierce reported at the annual meeting of the Pediatric Academic Societies.

“One important limitation to this study is that it’s difficult to assess bronchiolitis severity in each of our groups, so there could have been seasonal variations that may have affected our outcomes,” he said. “Our after-implementation group is larger than our before-implementation group, and it’s hard to tell if that’s due to a seasonal increase in bronchiolitis cases, or if there was just higher use of HFNC on patients once it was allowed in the general wards.”

Demographic information was collected from the hospital billing database on subjects’ age, race, sex, and secondhand smoke exposure and whether they had public or private insurance. Although there was a statistically significant difference in age between the groups – 3 months before March 2012, 5 months after – the other demographic data were largely consistent from before implementation to after.

Dr. Fierce did not report any relevant financial disclosures.

[email protected]

SAN DIEGO – Missed vaccination opportunities are common among adolescents with chronic medical conditions, especially for the first human papillomavirus (HPV) vaccine dose and for those who require the pneumococcal polysaccharide vaccination, an urban-based retrospective analysis showed.

“There are surprisingly little data describing routine vaccination coverage and missed opportunities for vaccination among the growing population of adolescents with chronic medical conditions,” Dr. Annika M. Hofstetter said in an interview in advance of the annual meeting of the Pediatric Academic Societies. “This study was unique in that it examined all recommended vaccines for adolescents with chronic medical conditions. A particular strength was the use of a large hospital immunization information system linked with other databases containing demographic, visit, and clinical information relevant to vaccination.”

Dr. Hofstetter, who conducted the study with colleagues while a faculty member in the department of pediatrics at Columbia University, New York, evaluated the records of 3,989 patients aged 11-17 years who received care at one of four clinics affiliated with the university between August 2011 and June 2013. The researchers used ICD-9 codes to identify adolescents with chronic medical conditions and chi square analysis to compare vaccination coverage and missed opportunities for vaccination among those with and without chronic medical conditions. They also used multivariable logistic regression to evaluate the impact of demographic and visit characteristics on vaccination outcomes.

Dr. Hofstetter, now a pediatrician at Seattle Children’s Hospital and the University of Washington, reported that 97% of the adolescents were nonwhite, 60% spoke Spanish, and 82% were publicly insured.

Fewer adolescents with chronic medical conditions had initiated HPV vaccination, compared with their healthy counterparts (81% vs. 85%, respectively), yet a higher percentage had received influenza vaccine during the 2012-2013 season (74% vs. 64%), “although still suboptimal,” the researchers wrote in their abstract. Other routine vaccination coverage was similar between groups (about 97% for tetanus/diphtheria/pertussis; 94% for meningococcal vaccine, and 58% for three or more doses of HPV vaccine).

Missed opportunities for routine vaccination were higher among adolescents with chronic medical conditions, compared with their healthy counterparts (47% vs. 41%), as were missed opportunities for initiating HPV vaccination at visits where other needed vaccines were administered (63% vs. 52%).

When the researchers limited the analysis to adolescents with chronic medical conditions, they found that subspecialty care was inversely associated with HPV vaccination and had no impact on influenza vaccination. Among those who required a pneumococcal polysaccharide vaccination as per Advisory Committee of Immunization Practices recommendations, only 36% had received a dose in their lifetime. Most (91%) had one or more missed opportunities to receive the pneumococcal polysaccharide vaccine.

“Missed opportunities for vaccination of adolescents with chronic medical conditions were common,” Dr. Hofstetter concluded. “Strategies that act to reduce missed opportunities and enhance uptake for these at-risk adolescents are needed. Specifically, it will be important to focus on: 1) improving rates of HPV vaccination initiation among boys with chronic medical conditions; 2) optimizing influenza vaccination of adolescents with chronic medical conditions since, although they had higher rates than their healthy counterparts, they are at increased risk of influenza-associated complications; and 3) increasing the markedly low pneumococcal polysaccharide vaccination coverage of eligible patients.”

She acknowledged certain limitations of the study, including the fact that it focused solely on low-income minority patients attending four urban pediatric clinics with high baseline vaccination coverage. “Thus, the findings may be less generalizable to other populations and settings across the country,” she said.

This investigator-initiated study was supported in part by the Pfizer Medical Education Group. Dr. Hofstetter disclosed that she previously received research support for another investigator-initiated study from the Merck Investigator Studies Program.

[email protected]

On Twitter @dougbrunk

SAN DIEGO – Missed vaccination opportunities are common among adolescents with chronic medical conditions, especially for the first human papillomavirus (HPV) vaccine dose and for those who require the pneumococcal polysaccharide vaccination, an urban-based retrospective analysis showed.

“There are surprisingly little data describing routine vaccination coverage and missed opportunities for vaccination among the growing population of adolescents with chronic medical conditions,” Dr. Annika M. Hofstetter said in an interview in advance of the annual meeting of the Pediatric Academic Societies. “This study was unique in that it examined all recommended vaccines for adolescents with chronic medical conditions. A particular strength was the use of a large hospital immunization information system linked with other databases containing demographic, visit, and clinical information relevant to vaccination.”

Dr. Hofstetter, who conducted the study with colleagues while a faculty member in the department of pediatrics at Columbia University, New York, evaluated the records of 3,989 patients aged 11-17 years who received care at one of four clinics affiliated with the university between August 2011 and June 2013. The researchers used ICD-9 codes to identify adolescents with chronic medical conditions and chi square analysis to compare vaccination coverage and missed opportunities for vaccination among those with and without chronic medical conditions. They also used multivariable logistic regression to evaluate the impact of demographic and visit characteristics on vaccination outcomes.

Dr. Hofstetter, now a pediatrician at Seattle Children’s Hospital and the University of Washington, reported that 97% of the adolescents were nonwhite, 60% spoke Spanish, and 82% were publicly insured.

Fewer adolescents with chronic medical conditions had initiated HPV vaccination, compared with their healthy counterparts (81% vs. 85%, respectively), yet a higher percentage had received influenza vaccine during the 2012-2013 season (74% vs. 64%), “although still suboptimal,” the researchers wrote in their abstract. Other routine vaccination coverage was similar between groups (about 97% for tetanus/diphtheria/pertussis; 94% for meningococcal vaccine, and 58% for three or more doses of HPV vaccine).

Missed opportunities for routine vaccination were higher among adolescents with chronic medical conditions, compared with their healthy counterparts (47% vs. 41%), as were missed opportunities for initiating HPV vaccination at visits where other needed vaccines were administered (63% vs. 52%).

When the researchers limited the analysis to adolescents with chronic medical conditions, they found that subspecialty care was inversely associated with HPV vaccination and had no impact on influenza vaccination. Among those who required a pneumococcal polysaccharide vaccination as per Advisory Committee of Immunization Practices recommendations, only 36% had received a dose in their lifetime. Most (91%) had one or more missed opportunities to receive the pneumococcal polysaccharide vaccine.

“Missed opportunities for vaccination of adolescents with chronic medical conditions were common,” Dr. Hofstetter concluded. “Strategies that act to reduce missed opportunities and enhance uptake for these at-risk adolescents are needed. Specifically, it will be important to focus on: 1) improving rates of HPV vaccination initiation among boys with chronic medical conditions; 2) optimizing influenza vaccination of adolescents with chronic medical conditions since, although they had higher rates than their healthy counterparts, they are at increased risk of influenza-associated complications; and 3) increasing the markedly low pneumococcal polysaccharide vaccination coverage of eligible patients.”

She acknowledged certain limitations of the study, including the fact that it focused solely on low-income minority patients attending four urban pediatric clinics with high baseline vaccination coverage. “Thus, the findings may be less generalizable to other populations and settings across the country,” she said.

This investigator-initiated study was supported in part by the Pfizer Medical Education Group. Dr. Hofstetter disclosed that she previously received research support for another investigator-initiated study from the Merck Investigator Studies Program.

[email protected]

On Twitter @dougbrunk

SAN DIEGO – Missed vaccination opportunities are common among adolescents with chronic medical conditions, especially for the first human papillomavirus (HPV) vaccine dose and for those who require the pneumococcal polysaccharide vaccination, an urban-based retrospective analysis showed.

“There are surprisingly little data describing routine vaccination coverage and missed opportunities for vaccination among the growing population of adolescents with chronic medical conditions,” Dr. Annika M. Hofstetter said in an interview in advance of the annual meeting of the Pediatric Academic Societies. “This study was unique in that it examined all recommended vaccines for adolescents with chronic medical conditions. A particular strength was the use of a large hospital immunization information system linked with other databases containing demographic, visit, and clinical information relevant to vaccination.”

Dr. Hofstetter, who conducted the study with colleagues while a faculty member in the department of pediatrics at Columbia University, New York, evaluated the records of 3,989 patients aged 11-17 years who received care at one of four clinics affiliated with the university between August 2011 and June 2013. The researchers used ICD-9 codes to identify adolescents with chronic medical conditions and chi square analysis to compare vaccination coverage and missed opportunities for vaccination among those with and without chronic medical conditions. They also used multivariable logistic regression to evaluate the impact of demographic and visit characteristics on vaccination outcomes.

Dr. Hofstetter, now a pediatrician at Seattle Children’s Hospital and the University of Washington, reported that 97% of the adolescents were nonwhite, 60% spoke Spanish, and 82% were publicly insured.

Fewer adolescents with chronic medical conditions had initiated HPV vaccination, compared with their healthy counterparts (81% vs. 85%, respectively), yet a higher percentage had received influenza vaccine during the 2012-2013 season (74% vs. 64%), “although still suboptimal,” the researchers wrote in their abstract. Other routine vaccination coverage was similar between groups (about 97% for tetanus/diphtheria/pertussis; 94% for meningococcal vaccine, and 58% for three or more doses of HPV vaccine).

Missed opportunities for routine vaccination were higher among adolescents with chronic medical conditions, compared with their healthy counterparts (47% vs. 41%), as were missed opportunities for initiating HPV vaccination at visits where other needed vaccines were administered (63% vs. 52%).

When the researchers limited the analysis to adolescents with chronic medical conditions, they found that subspecialty care was inversely associated with HPV vaccination and had no impact on influenza vaccination. Among those who required a pneumococcal polysaccharide vaccination as per Advisory Committee of Immunization Practices recommendations, only 36% had received a dose in their lifetime. Most (91%) had one or more missed opportunities to receive the pneumococcal polysaccharide vaccine.

“Missed opportunities for vaccination of adolescents with chronic medical conditions were common,” Dr. Hofstetter concluded. “Strategies that act to reduce missed opportunities and enhance uptake for these at-risk adolescents are needed. Specifically, it will be important to focus on: 1) improving rates of HPV vaccination initiation among boys with chronic medical conditions; 2) optimizing influenza vaccination of adolescents with chronic medical conditions since, although they had higher rates than their healthy counterparts, they are at increased risk of influenza-associated complications; and 3) increasing the markedly low pneumococcal polysaccharide vaccination coverage of eligible patients.”

She acknowledged certain limitations of the study, including the fact that it focused solely on low-income minority patients attending four urban pediatric clinics with high baseline vaccination coverage. “Thus, the findings may be less generalizable to other populations and settings across the country,” she said.

This investigator-initiated study was supported in part by the Pfizer Medical Education Group. Dr. Hofstetter disclosed that she previously received research support for another investigator-initiated study from the Merck Investigator Studies Program.

[email protected]

On Twitter @dougbrunk

GENEVA – The tests widely available today that use a cancer patient’s tumor DNA that circulates in the blood to detect a treatment-altering lung cancer mutation vary widely in sensitivity, meaning that using circulating DNA to identify a clinically important mutation should be limited to when biopsying the primary does not yield enough DNA for testing.

“It is important to use robust and sensitive methods” when trying to match treatment to the molecular specificities of each patient’s tumor, Dr. Martin Reck said at the European Lung Cancer Conference.

Mitchel L. Zoler/Frontline Medical News

Results from a study that prospectively compared DNA analysis for mutations in the epidermal growth factor receptor (EGFR) gene in tumor biopsies from 1,162 patients with advanced non–small cell lung cancer with DNA analysis of circulating tumor DNA (ctDNA) from the same patients showed that ctDNA analysis had 46% sensitivity, compared with tumor biopsy DNA, reported Dr. Reck, a thoracic oncologist at the Lung Clinic in Grosshandsdorf, Germany. This high level of false-negative results with ctDNA analysis produced a positive predictive value of 78%. In contrast, ctDNA has a specificity of 97% and a negative predictive value of 90%.

The results from the international study, which included 881 patients from seven European countries plus 281 patients from Japan, highlighted the divergent concordance among EGFR mutation comparisons of ctDNA and biopsy DNA depending on which DNA tests were used. Participating physicians could order whichever genetic analyses they wanted. A subanalysis of the study showed, for example, that among the 138 patients whose tumor and ctDNAs were both evaluated for EGFR mutations using the therascreen test marketed by QIAGEN the concordance rose to 95%, the sensitivity of ctDNA was 73%, and the positive predictive value was 94%, Dr. Reck reported.

The Europe-Japan Diagnostic Study for EGFR Testing (ASSESS) enrolled patients with either newly diagnosed, locally advanced stage IIIA or IIIB metastatic non–small cell lung cancer or patients with recurrent non–small cell lung cancer following surgical resection. Patients averaged about 67 years old, and about 85% had stage IV disease. The genetic analyses identified EGFR mutations in 31% of the Japanese patients and in 12% of those in Europe.

[email protected]

On Twitter @mitchelzoler

GENEVA – The tests widely available today that use a cancer patient’s tumor DNA that circulates in the blood to detect a treatment-altering lung cancer mutation vary widely in sensitivity, meaning that using circulating DNA to identify a clinically important mutation should be limited to when biopsying the primary does not yield enough DNA for testing.

“It is important to use robust and sensitive methods” when trying to match treatment to the molecular specificities of each patient’s tumor, Dr. Martin Reck said at the European Lung Cancer Conference.

Mitchel L. Zoler/Frontline Medical News

Results from a study that prospectively compared DNA analysis for mutations in the epidermal growth factor receptor (EGFR) gene in tumor biopsies from 1,162 patients with advanced non–small cell lung cancer with DNA analysis of circulating tumor DNA (ctDNA) from the same patients showed that ctDNA analysis had 46% sensitivity, compared with tumor biopsy DNA, reported Dr. Reck, a thoracic oncologist at the Lung Clinic in Grosshandsdorf, Germany. This high level of false-negative results with ctDNA analysis produced a positive predictive value of 78%. In contrast, ctDNA has a specificity of 97% and a negative predictive value of 90%.

The results from the international study, which included 881 patients from seven European countries plus 281 patients from Japan, highlighted the divergent concordance among EGFR mutation comparisons of ctDNA and biopsy DNA depending on which DNA tests were used. Participating physicians could order whichever genetic analyses they wanted. A subanalysis of the study showed, for example, that among the 138 patients whose tumor and ctDNAs were both evaluated for EGFR mutations using the therascreen test marketed by QIAGEN the concordance rose to 95%, the sensitivity of ctDNA was 73%, and the positive predictive value was 94%, Dr. Reck reported.

The Europe-Japan Diagnostic Study for EGFR Testing (ASSESS) enrolled patients with either newly diagnosed, locally advanced stage IIIA or IIIB metastatic non–small cell lung cancer or patients with recurrent non–small cell lung cancer following surgical resection. Patients averaged about 67 years old, and about 85% had stage IV disease. The genetic analyses identified EGFR mutations in 31% of the Japanese patients and in 12% of those in Europe.

[email protected]

On Twitter @mitchelzoler

GENEVA – The tests widely available today that use a cancer patient’s tumor DNA that circulates in the blood to detect a treatment-altering lung cancer mutation vary widely in sensitivity, meaning that using circulating DNA to identify a clinically important mutation should be limited to when biopsying the primary does not yield enough DNA for testing.

“It is important to use robust and sensitive methods” when trying to match treatment to the molecular specificities of each patient’s tumor, Dr. Martin Reck said at the European Lung Cancer Conference.

Mitchel L. Zoler/Frontline Medical News

Results from a study that prospectively compared DNA analysis for mutations in the epidermal growth factor receptor (EGFR) gene in tumor biopsies from 1,162 patients with advanced non–small cell lung cancer with DNA analysis of circulating tumor DNA (ctDNA) from the same patients showed that ctDNA analysis had 46% sensitivity, compared with tumor biopsy DNA, reported Dr. Reck, a thoracic oncologist at the Lung Clinic in Grosshandsdorf, Germany. This high level of false-negative results with ctDNA analysis produced a positive predictive value of 78%. In contrast, ctDNA has a specificity of 97% and a negative predictive value of 90%.

The results from the international study, which included 881 patients from seven European countries plus 281 patients from Japan, highlighted the divergent concordance among EGFR mutation comparisons of ctDNA and biopsy DNA depending on which DNA tests were used. Participating physicians could order whichever genetic analyses they wanted. A subanalysis of the study showed, for example, that among the 138 patients whose tumor and ctDNAs were both evaluated for EGFR mutations using the therascreen test marketed by QIAGEN the concordance rose to 95%, the sensitivity of ctDNA was 73%, and the positive predictive value was 94%, Dr. Reck reported.

The Europe-Japan Diagnostic Study for EGFR Testing (ASSESS) enrolled patients with either newly diagnosed, locally advanced stage IIIA or IIIB metastatic non–small cell lung cancer or patients with recurrent non–small cell lung cancer following surgical resection. Patients averaged about 67 years old, and about 85% had stage IV disease. The genetic analyses identified EGFR mutations in 31% of the Japanese patients and in 12% of those in Europe.

[email protected]

On Twitter @mitchelzoler

A marked rise in pertussis cases in recent years is a result of the accumulated effects of switching from whole-cell to acellular pertussis vaccine in the 1990s, and not declining vaccination rates, according to epidemiological modeling published online April 23 in PLOS Computational Biology.

Since the 1990s, the incidence of pertussis in the United States has risen steadily, with 2012 seeing the highest number of cases since 1955, shortly after pertussis vaccine was introduced. Infants have continued to have the highest number of reported cases, but there also has been a recent shift in disease burden from adolescents to 7- to 11-year-olds, researchers noted.

©luiscar/Thinkstockphotos.com

Vaccination coverage, however, has remained robust for decades, at greater than 90%. What has changed is that the whole-cell pertussis component of the DTP vaccine was phased out in the 1990s due to convulsions and other safety issues and replaced by the acellular component in the DTaP.

That turned out to be the key when investigators from the Centers for Disease Control and Prevention and elsewhere ran a series of computer models to explain the upsurge in cases.

The model that best fit decades of actual incidence data from the CDC and other sources estimated 90% vaccine efficacy with the whole-cell series and essentially life-long protection but 80% efficacy with the acellular series and an average of 50 years of protection, meaning that some people become vulnerable to infection sooner (PLoS Comput. Biol. 2015 April 23 [doi:10.1371/journal.pcbi.1004138]).

Those differences reproduced “the trends in the … incidence data up to 2009; running the model forward over another three years shows a continued correspondence with observed incidence trends. Relatively small differences in the per-dose vaccine efficacy and duration of protection between acellular and whole-cell vaccines is sufficient to explain the recent upsurge in pertussis in the United States,” as well as the age-distribution shift, said the authors, led by Dr. Manoj Gambhir, a mathematical epidemiologist of Monash University, Melbourne, who is working with the CDC.

“Vaccine-induced immunity [with DTaP] wanes faster than previously thought … adults and adolescents may be an important reservoir of infection. Future refinement of the model … will allow for an exploration of alternative vaccination age-spacings for the five-dose childhood schedule; investigation into the effects of further booster doses (for example, decennially to adults); and cocooning vaccination strategies designed to protect infants who are most vulnerable to severe disease. … Booster doses may be sufficient to curtail epidemics while vaccine research continues,” they concluded.

Although pertussis mutation may be contributing to the problem, other reasons proposed for the upswing in cases – including increased reporting and changes in contact patterns between infected and healthy kids – are “not necessary to explain recent patterns in pertussis incidence,” the investigators noted.

The work was funded by the U.S. National Institutes of Health, the UK Medical Research Council, and the UK National Institute of Health Research. Dr. Gambhir is an employee of IHRC; the remaining authors have no relevant financial disclosures.

[email protected]

A marked rise in pertussis cases in recent years is a result of the accumulated effects of switching from whole-cell to acellular pertussis vaccine in the 1990s, and not declining vaccination rates, according to epidemiological modeling published online April 23 in PLOS Computational Biology.

Since the 1990s, the incidence of pertussis in the United States has risen steadily, with 2012 seeing the highest number of cases since 1955, shortly after pertussis vaccine was introduced. Infants have continued to have the highest number of reported cases, but there also has been a recent shift in disease burden from adolescents to 7- to 11-year-olds, researchers noted.

©luiscar/Thinkstockphotos.com

Vaccination coverage, however, has remained robust for decades, at greater than 90%. What has changed is that the whole-cell pertussis component of the DTP vaccine was phased out in the 1990s due to convulsions and other safety issues and replaced by the acellular component in the DTaP.

That turned out to be the key when investigators from the Centers for Disease Control and Prevention and elsewhere ran a series of computer models to explain the upsurge in cases.

The model that best fit decades of actual incidence data from the CDC and other sources estimated 90% vaccine efficacy with the whole-cell series and essentially life-long protection but 80% efficacy with the acellular series and an average of 50 years of protection, meaning that some people become vulnerable to infection sooner (PLoS Comput. Biol. 2015 April 23 [doi:10.1371/journal.pcbi.1004138]).

Those differences reproduced “the trends in the … incidence data up to 2009; running the model forward over another three years shows a continued correspondence with observed incidence trends. Relatively small differences in the per-dose vaccine efficacy and duration of protection between acellular and whole-cell vaccines is sufficient to explain the recent upsurge in pertussis in the United States,” as well as the age-distribution shift, said the authors, led by Dr. Manoj Gambhir, a mathematical epidemiologist of Monash University, Melbourne, who is working with the CDC.

“Vaccine-induced immunity [with DTaP] wanes faster than previously thought … adults and adolescents may be an important reservoir of infection. Future refinement of the model … will allow for an exploration of alternative vaccination age-spacings for the five-dose childhood schedule; investigation into the effects of further booster doses (for example, decennially to adults); and cocooning vaccination strategies designed to protect infants who are most vulnerable to severe disease. … Booster doses may be sufficient to curtail epidemics while vaccine research continues,” they concluded.

Although pertussis mutation may be contributing to the problem, other reasons proposed for the upswing in cases – including increased reporting and changes in contact patterns between infected and healthy kids – are “not necessary to explain recent patterns in pertussis incidence,” the investigators noted.

The work was funded by the U.S. National Institutes of Health, the UK Medical Research Council, and the UK National Institute of Health Research. Dr. Gambhir is an employee of IHRC; the remaining authors have no relevant financial disclosures.

[email protected]

A marked rise in pertussis cases in recent years is a result of the accumulated effects of switching from whole-cell to acellular pertussis vaccine in the 1990s, and not declining vaccination rates, according to epidemiological modeling published online April 23 in PLOS Computational Biology.

Since the 1990s, the incidence of pertussis in the United States has risen steadily, with 2012 seeing the highest number of cases since 1955, shortly after pertussis vaccine was introduced. Infants have continued to have the highest number of reported cases, but there also has been a recent shift in disease burden from adolescents to 7- to 11-year-olds, researchers noted.

©luiscar/Thinkstockphotos.com

Vaccination coverage, however, has remained robust for decades, at greater than 90%. What has changed is that the whole-cell pertussis component of the DTP vaccine was phased out in the 1990s due to convulsions and other safety issues and replaced by the acellular component in the DTaP.

That turned out to be the key when investigators from the Centers for Disease Control and Prevention and elsewhere ran a series of computer models to explain the upsurge in cases.

The model that best fit decades of actual incidence data from the CDC and other sources estimated 90% vaccine efficacy with the whole-cell series and essentially life-long protection but 80% efficacy with the acellular series and an average of 50 years of protection, meaning that some people become vulnerable to infection sooner (PLoS Comput. Biol. 2015 April 23 [doi:10.1371/journal.pcbi.1004138]).

Those differences reproduced “the trends in the … incidence data up to 2009; running the model forward over another three years shows a continued correspondence with observed incidence trends. Relatively small differences in the per-dose vaccine efficacy and duration of protection between acellular and whole-cell vaccines is sufficient to explain the recent upsurge in pertussis in the United States,” as well as the age-distribution shift, said the authors, led by Dr. Manoj Gambhir, a mathematical epidemiologist of Monash University, Melbourne, who is working with the CDC.

“Vaccine-induced immunity [with DTaP] wanes faster than previously thought … adults and adolescents may be an important reservoir of infection. Future refinement of the model … will allow for an exploration of alternative vaccination age-spacings for the five-dose childhood schedule; investigation into the effects of further booster doses (for example, decennially to adults); and cocooning vaccination strategies designed to protect infants who are most vulnerable to severe disease. … Booster doses may be sufficient to curtail epidemics while vaccine research continues,” they concluded.

Although pertussis mutation may be contributing to the problem, other reasons proposed for the upswing in cases – including increased reporting and changes in contact patterns between infected and healthy kids – are “not necessary to explain recent patterns in pertussis incidence,” the investigators noted.

The work was funded by the U.S. National Institutes of Health, the UK Medical Research Council, and the UK National Institute of Health Research. Dr. Gambhir is an employee of IHRC; the remaining authors have no relevant financial disclosures.

[email protected]

CHICAGO– Helping patients quit smoking, whether those with severe mental illness or comorbid depression, is an “excellent opportunity” for primary care doctors and psychiatrists to work together.

That’s according to Dr. Robert M. Anthenelli, a professor of psychiatry at the University of California, San Diego, and director of the Pacific Treatment and Research Center there.

Depression and smoking are often comorbid in patients, and nearly half of all tobacco products consumed in the United States are done so by people with some form of a psychiatric or other substance use disorder. In this interview, recorded at the meeting, sponsored by Current Psychiatry and American Academy of Clinical Psychiatrists, Dr. Anthenelli discusses brain changes in tobacco use, why there is a link between smoking and mental illness, and what primary care physicians can do to help their patients who smoke. He also addresses whether complete cessation is essential to one’s well-being.

Dr. Anthenelli is a consultant to Pfizer and Arena Pharmaceuticals.

Current Psychiatry and this news organization are owned by the same parent company.

[email protected]

On Twitter @whitneymcknight

CHICAGO– Helping patients quit smoking, whether those with severe mental illness or comorbid depression, is an “excellent opportunity” for primary care doctors and psychiatrists to work together.

That’s according to Dr. Robert M. Anthenelli, a professor of psychiatry at the University of California, San Diego, and director of the Pacific Treatment and Research Center there.

Depression and smoking are often comorbid in patients, and nearly half of all tobacco products consumed in the United States are done so by people with some form of a psychiatric or other substance use disorder. In this interview, recorded at the meeting, sponsored by Current Psychiatry and American Academy of Clinical Psychiatrists, Dr. Anthenelli discusses brain changes in tobacco use, why there is a link between smoking and mental illness, and what primary care physicians can do to help their patients who smoke. He also addresses whether complete cessation is essential to one’s well-being.

Dr. Anthenelli is a consultant to Pfizer and Arena Pharmaceuticals.

Current Psychiatry and this news organization are owned by the same parent company.

[email protected]

On Twitter @whitneymcknight

CHICAGO– Helping patients quit smoking, whether those with severe mental illness or comorbid depression, is an “excellent opportunity” for primary care doctors and psychiatrists to work together.

That’s according to Dr. Robert M. Anthenelli, a professor of psychiatry at the University of California, San Diego, and director of the Pacific Treatment and Research Center there.

Depression and smoking are often comorbid in patients, and nearly half of all tobacco products consumed in the United States are done so by people with some form of a psychiatric or other substance use disorder. In this interview, recorded at the meeting, sponsored by Current Psychiatry and American Academy of Clinical Psychiatrists, Dr. Anthenelli discusses brain changes in tobacco use, why there is a link between smoking and mental illness, and what primary care physicians can do to help their patients who smoke. He also addresses whether complete cessation is essential to one’s well-being.

Dr. Anthenelli is a consultant to Pfizer and Arena Pharmaceuticals.

Current Psychiatry and this news organization are owned by the same parent company.

[email protected]

On Twitter @whitneymcknight

HOUSTON – The number needed to treat with Timothy grass sublingual immunotherapy tablets for allergic rhinitis to achieve a clinically meaningful response is 7.9, Dr. Stephen R. Durham reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

What the low number needed to treat (NNT) means in this instance is that, on average, 7.9 children or adults with Timothy grass–induced allergic rhinitis with or without conjunctivitis would need to be treated with Merck’s sublingual immunotherapy tablet (SLIT) rather than placebo daily for 3 years in order for 1 additional patient to obtain sustained benefit. Sustained benefit was defined as at least 50% well days for the entire grass pollen season during each of the 3 treatment years plus the subsequent 2 years of no treatment, explained Dr. Durham of Royal Brompton and Harefield Hospitals and Imperial College, London.

© PeskyMonkey/iStockphoto.com

A ‘well day’ was considered as a day with no use of open-label rescue medication and in which the worst score recorded was ‘none’ or ‘mild’ for each of the four nasal and two ocular symptoms measured. This NNT analysis was based upon pooled data from six pivotal randomized, double-blind, phase III, placebo-controlled clinical trials totaling 3,094 patients, Dr. Durham added.

A separate analysis of the same pooled data using a different definition of favorable response – that is, a total combined daily symptom and daily medication score of 3 or less during the entire grass pollen season during the 3 treatment years, plus the following 2 no-treatment years – yielded an NNT of 9.4. The maximum total daily symptom score during any given year was 18, while the maximum daily medication score per year was 30-36, depending upon whether the participant was a child or adult, and whether the study was conducted in Europe or the United States.

The risk-benefit ratio of SLIT for allergic rhinitis in the pooled analysis was favorable as reflected in a number needed to harm of 303, with harm defined as a treatment-related systemic allergic reaction. When the NNH was recalculated using epinephrine usage as the harmful endpoint, the NNH was closely similar at 305.

Merck’s Timothy grass SLIT, marketed as Grastek, is FDA-approved for treatment of allergic rhinitis in adults and children as young as 5 years of age.

Dr. Durham reported receiving research grants and serving as a consultant to Merck, ALK, and Stallergenes. The NNT analysis was funded by Merck, and the phase III clinical trials on which the analysis was based were supported by ALK and Merck.

[email protected]

HOUSTON – The number needed to treat with Timothy grass sublingual immunotherapy tablets for allergic rhinitis to achieve a clinically meaningful response is 7.9, Dr. Stephen R. Durham reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

What the low number needed to treat (NNT) means in this instance is that, on average, 7.9 children or adults with Timothy grass–induced allergic rhinitis with or without conjunctivitis would need to be treated with Merck’s sublingual immunotherapy tablet (SLIT) rather than placebo daily for 3 years in order for 1 additional patient to obtain sustained benefit. Sustained benefit was defined as at least 50% well days for the entire grass pollen season during each of the 3 treatment years plus the subsequent 2 years of no treatment, explained Dr. Durham of Royal Brompton and Harefield Hospitals and Imperial College, London.

© PeskyMonkey/iStockphoto.com

A ‘well day’ was considered as a day with no use of open-label rescue medication and in which the worst score recorded was ‘none’ or ‘mild’ for each of the four nasal and two ocular symptoms measured. This NNT analysis was based upon pooled data from six pivotal randomized, double-blind, phase III, placebo-controlled clinical trials totaling 3,094 patients, Dr. Durham added.

A separate analysis of the same pooled data using a different definition of favorable response – that is, a total combined daily symptom and daily medication score of 3 or less during the entire grass pollen season during the 3 treatment years, plus the following 2 no-treatment years – yielded an NNT of 9.4. The maximum total daily symptom score during any given year was 18, while the maximum daily medication score per year was 30-36, depending upon whether the participant was a child or adult, and whether the study was conducted in Europe or the United States.

The risk-benefit ratio of SLIT for allergic rhinitis in the pooled analysis was favorable as reflected in a number needed to harm of 303, with harm defined as a treatment-related systemic allergic reaction. When the NNH was recalculated using epinephrine usage as the harmful endpoint, the NNH was closely similar at 305.

Merck’s Timothy grass SLIT, marketed as Grastek, is FDA-approved for treatment of allergic rhinitis in adults and children as young as 5 years of age.

Dr. Durham reported receiving research grants and serving as a consultant to Merck, ALK, and Stallergenes. The NNT analysis was funded by Merck, and the phase III clinical trials on which the analysis was based were supported by ALK and Merck.

[email protected]

HOUSTON – The number needed to treat with Timothy grass sublingual immunotherapy tablets for allergic rhinitis to achieve a clinically meaningful response is 7.9, Dr. Stephen R. Durham reported at the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

What the low number needed to treat (NNT) means in this instance is that, on average, 7.9 children or adults with Timothy grass–induced allergic rhinitis with or without conjunctivitis would need to be treated with Merck’s sublingual immunotherapy tablet (SLIT) rather than placebo daily for 3 years in order for 1 additional patient to obtain sustained benefit. Sustained benefit was defined as at least 50% well days for the entire grass pollen season during each of the 3 treatment years plus the subsequent 2 years of no treatment, explained Dr. Durham of Royal Brompton and Harefield Hospitals and Imperial College, London.

© PeskyMonkey/iStockphoto.com

A ‘well day’ was considered as a day with no use of open-label rescue medication and in which the worst score recorded was ‘none’ or ‘mild’ for each of the four nasal and two ocular symptoms measured. This NNT analysis was based upon pooled data from six pivotal randomized, double-blind, phase III, placebo-controlled clinical trials totaling 3,094 patients, Dr. Durham added.

A separate analysis of the same pooled data using a different definition of favorable response – that is, a total combined daily symptom and daily medication score of 3 or less during the entire grass pollen season during the 3 treatment years, plus the following 2 no-treatment years – yielded an NNT of 9.4. The maximum total daily symptom score during any given year was 18, while the maximum daily medication score per year was 30-36, depending upon whether the participant was a child or adult, and whether the study was conducted in Europe or the United States.

The risk-benefit ratio of SLIT for allergic rhinitis in the pooled analysis was favorable as reflected in a number needed to harm of 303, with harm defined as a treatment-related systemic allergic reaction. When the NNH was recalculated using epinephrine usage as the harmful endpoint, the NNH was closely similar at 305.

Merck’s Timothy grass SLIT, marketed as Grastek, is FDA-approved for treatment of allergic rhinitis in adults and children as young as 5 years of age.

Dr. Durham reported receiving research grants and serving as a consultant to Merck, ALK, and Stallergenes. The NNT analysis was funded by Merck, and the phase III clinical trials on which the analysis was based were supported by ALK and Merck.

[email protected]

The American College of Chest Physicians and the Canadian Thoracic Society have issued new recommendations for reducing the risk of acute exacerbations of COPD.

The guideline, representing the first partnership of its kind between two of the largest thoracic societies in the world, includes 33 recommendations based on “an up-to-date, rigorous, evidence-based analysis of current randomized controlled trial data,” according to Dr. Gerard J. Criner, professor of pulmonary and critical care medicine, Temple University, Philadelphia, and his associates on the guideline’s expert panel.

“Exacerbations are to COPD what myocardial infarctions are to coronary artery disease: They are acute, trajectory changing, and often deadly manifestations of a chronic disease. Exacerbations cause frequent hospital admissions, relapses, and readmissions; contribute to death during hospitalization or shortly thereafter; reduce quality of life dramatically; consume financial resources; and hasten a progressive decline in pulmonary function, a cardinal feature of COPD,” Dr. Criner and his associates wrote (CHEST 2015;147:894-942).

Current COPD treatment guidelines state that prevention of exacerbations is possible, but they provide little guidance to clinicians regarding available therapies. The ACCP and CTS jointly commissioned their guideline to address “this important void in COPD management.”

Among their recommendations are the following:

• Patients with moderate, severe, or very severe COPD who had an exacerbation within the preceding 4 weeks should undergo pulmonary rehabilitation to prevent further exacerbations. In contrast, the data do not support pulmonary rehabilitation for those whose most recent exacerbation was more than 4 weeks earlier.

• Smoking cessation counseling and treatment are suggested as a component of a comprehensive clinical strategy to prevent COPD exacerbations. Quitting smoking is the only evidence-based intervention that actually improves COPD prognosis, because it mitigates further declines in lung function and reduces symptoms.

• Education plus case management together, to include direct contact with a health care specialist at least monthly, are recommended to prevent acute exacerbations; either measure alone is insufficient to reduce exacerbations.

• Administration of the 23-valent pneumococcal vaccine is suggested even though evidence does not specifically support the vaccine for preventing acute exacerbations. Rather, the vaccine benefits the general health of people aged 65 and older and of all adults who have underlying chronic medical conditions such as COPD.

• Annual administration of the influenza vaccine is recommended because of its benefit regarding general health and the fact that existing guidelines recommend it for COPD patients.

The guideline also addresses the use of numerous medications, alone or in combination, in great detail, including short- and long-acting beta-2 agonists, short- and long-acting muscarinic antagonists, inhaled corticosteroids, inhaled long-acting anticholinergics, long-term macrolides, oral and IV systemic corticosteroids, roflumilast (when chronic bronchitis is present), oral slow-release theophylline, oral N-acetylcysteine, oral carbocysteine, and statins.

There is a section on novel therapies, including agents that target airway inflammation such as adenosine A2A-receptor agonists, inhibitors of proinflammatory pathways, and activators of anti-inflammatory pathways. Other new approaches include drugs with antioxidant effects, drugs that facilitate lung regeneration, and mucoactive agents.

The American College of Chest Physicians and the Canadian Thoracic Society have issued new recommendations for reducing the risk of acute exacerbations of COPD.

The guideline, representing the first partnership of its kind between two of the largest thoracic societies in the world, includes 33 recommendations based on “an up-to-date, rigorous, evidence-based analysis of current randomized controlled trial data,” according to Dr. Gerard J. Criner, professor of pulmonary and critical care medicine, Temple University, Philadelphia, and his associates on the guideline’s expert panel.

“Exacerbations are to COPD what myocardial infarctions are to coronary artery disease: They are acute, trajectory changing, and often deadly manifestations of a chronic disease. Exacerbations cause frequent hospital admissions, relapses, and readmissions; contribute to death during hospitalization or shortly thereafter; reduce quality of life dramatically; consume financial resources; and hasten a progressive decline in pulmonary function, a cardinal feature of COPD,” Dr. Criner and his associates wrote (CHEST 2015;147:894-942).

Current COPD treatment guidelines state that prevention of exacerbations is possible, but they provide little guidance to clinicians regarding available therapies. The ACCP and CTS jointly commissioned their guideline to address “this important void in COPD management.”

Among their recommendations are the following:

• Patients with moderate, severe, or very severe COPD who had an exacerbation within the preceding 4 weeks should undergo pulmonary rehabilitation to prevent further exacerbations. In contrast, the data do not support pulmonary rehabilitation for those whose most recent exacerbation was more than 4 weeks earlier.

• Smoking cessation counseling and treatment are suggested as a component of a comprehensive clinical strategy to prevent COPD exacerbations. Quitting smoking is the only evidence-based intervention that actually improves COPD prognosis, because it mitigates further declines in lung function and reduces symptoms.

• Education plus case management together, to include direct contact with a health care specialist at least monthly, are recommended to prevent acute exacerbations; either measure alone is insufficient to reduce exacerbations.

• Administration of the 23-valent pneumococcal vaccine is suggested even though evidence does not specifically support the vaccine for preventing acute exacerbations. Rather, the vaccine benefits the general health of people aged 65 and older and of all adults who have underlying chronic medical conditions such as COPD.

• Annual administration of the influenza vaccine is recommended because of its benefit regarding general health and the fact that existing guidelines recommend it for COPD patients.

The guideline also addresses the use of numerous medications, alone or in combination, in great detail, including short- and long-acting beta-2 agonists, short- and long-acting muscarinic antagonists, inhaled corticosteroids, inhaled long-acting anticholinergics, long-term macrolides, oral and IV systemic corticosteroids, roflumilast (when chronic bronchitis is present), oral slow-release theophylline, oral N-acetylcysteine, oral carbocysteine, and statins.

There is a section on novel therapies, including agents that target airway inflammation such as adenosine A2A-receptor agonists, inhibitors of proinflammatory pathways, and activators of anti-inflammatory pathways. Other new approaches include drugs with antioxidant effects, drugs that facilitate lung regeneration, and mucoactive agents.

The American College of Chest Physicians and the Canadian Thoracic Society have issued new recommendations for reducing the risk of acute exacerbations of COPD.

The guideline, representing the first partnership of its kind between two of the largest thoracic societies in the world, includes 33 recommendations based on “an up-to-date, rigorous, evidence-based analysis of current randomized controlled trial data,” according to Dr. Gerard J. Criner, professor of pulmonary and critical care medicine, Temple University, Philadelphia, and his associates on the guideline’s expert panel.

“Exacerbations are to COPD what myocardial infarctions are to coronary artery disease: They are acute, trajectory changing, and often deadly manifestations of a chronic disease. Exacerbations cause frequent hospital admissions, relapses, and readmissions; contribute to death during hospitalization or shortly thereafter; reduce quality of life dramatically; consume financial resources; and hasten a progressive decline in pulmonary function, a cardinal feature of COPD,” Dr. Criner and his associates wrote (CHEST 2015;147:894-942).

Current COPD treatment guidelines state that prevention of exacerbations is possible, but they provide little guidance to clinicians regarding available therapies. The ACCP and CTS jointly commissioned their guideline to address “this important void in COPD management.”

Among their recommendations are the following:

• Patients with moderate, severe, or very severe COPD who had an exacerbation within the preceding 4 weeks should undergo pulmonary rehabilitation to prevent further exacerbations. In contrast, the data do not support pulmonary rehabilitation for those whose most recent exacerbation was more than 4 weeks earlier.

• Smoking cessation counseling and treatment are suggested as a component of a comprehensive clinical strategy to prevent COPD exacerbations. Quitting smoking is the only evidence-based intervention that actually improves COPD prognosis, because it mitigates further declines in lung function and reduces symptoms.

• Education plus case management together, to include direct contact with a health care specialist at least monthly, are recommended to prevent acute exacerbations; either measure alone is insufficient to reduce exacerbations.

• Administration of the 23-valent pneumococcal vaccine is suggested even though evidence does not specifically support the vaccine for preventing acute exacerbations. Rather, the vaccine benefits the general health of people aged 65 and older and of all adults who have underlying chronic medical conditions such as COPD.

• Annual administration of the influenza vaccine is recommended because of its benefit regarding general health and the fact that existing guidelines recommend it for COPD patients.

The guideline also addresses the use of numerous medications, alone or in combination, in great detail, including short- and long-acting beta-2 agonists, short- and long-acting muscarinic antagonists, inhaled corticosteroids, inhaled long-acting anticholinergics, long-term macrolides, oral and IV systemic corticosteroids, roflumilast (when chronic bronchitis is present), oral slow-release theophylline, oral N-acetylcysteine, oral carbocysteine, and statins.

There is a section on novel therapies, including agents that target airway inflammation such as adenosine A2A-receptor agonists, inhibitors of proinflammatory pathways, and activators of anti-inflammatory pathways. Other new approaches include drugs with antioxidant effects, drugs that facilitate lung regeneration, and mucoactive agents.

Malignant mesothelioma poses a significant challenge for clinicians because of its ability to resist chemotherapy, but the use of three-dimensional tumor spheroid models has shown that local administration of paclitaxel in a nanoparticle platform achieved better tumor penetration than conventional paclitaxel therapy, investigators reported. The study is in the May issue of the Journal of Thoracic and Cardiovascular Surgery.

Dr. Hongyi Lei of Brigham and Women’s Hospital, Boston, and his colleagues used the in vitro mesothelioma spheroid model because two-dimensional in vitro monolayer cell culture experiments do not replicate the superior efficacy of paclitaxel-loaded expansile nanoparticles (Pax-eNPs), suggesting that Pax-eNPs utilize a unique drug delivery mechanism.

Courtesy of AATS

The study observed that spheroids treated with Pax-eNP showed increased drug penetration and a 38-fold higher intraspheroidal drug concentration at 24 hours than that of paclitaxel dissolved in Cremophor EL/ethanol (J. Thorac. Cardiovasc. Surg. 2014 [doi:10.1016/j.jtcvs.2015.02.020]).

The researchers said their findings showed that three-dimensional spheroid models “are valuable tools for investigating cytotoxic mechanisms and nanoparticle-tumor interactions, particularly given the costs and limitations of in vivo animal studies.” Their findings were first presented at the 94th Annual Meeting of the American Association of Thoracic Surgery last year in Toronto.

Despite advances of nanoparticle-based drug delivery systems, difficulties in evaluating the effectiveness of these drugs in local chemotherapy have hindered their adoption in the clinic. Studies of the same agent utilizing in vitro vs. in vivo methods have shown conflicting results.

The observation that Pax-eNP treatment of intraperitoneal mesothelioma significantly improved survival in lab animals in vivo compared to conventional paclitaxel led to the use of the three-dimensional spheroid model. Dr. Lei and colleagues called this revelation “striking” because Pax-eNP exposure of the identical mesothelioma tumor cells plated as a two-dimensional monolayer in vitro demonstrated equal or worse results. “This suggested that eNP may be more effective at penetration and/or persistence within multicellular tumors and led to the use of a 3-D tumor spheroid mode,” they said.

“Given the high cost and limitations of in vivo animal studies, spheroid models may present a clinically relevant platform for screening novel pharmaceuticals and unique drug-delivery systems during the preclinical phase,” the researchers indicated.

They also investigated spheroid cytotoxicity in a clinic-like setting following a 4-hour, high-dose (1,000 ng/mL) paclitaxel exposure via conventional and eNP vehicles. They found that Pax-eNP exposure led to greater tumor cytotoxicity at 72 hours, and that cytotoxicity continued seven days later because Pax-eNPs rapidly enter the tumor spheroid and remain intracellular, slowly releasing the drug.

“The prolonged drug release mechanism that pH-triggered Pax-eNP uses appears to be unique, leading to markedly higher intraspheroidal drug delivery, prolonged intratumoral drug release and superior antitumor efficacy,” the investigators concluded. The authors had no disclosures.

Malignant mesothelioma poses a significant challenge for clinicians because of its ability to resist chemotherapy, but the use of three-dimensional tumor spheroid models has shown that local administration of paclitaxel in a nanoparticle platform achieved better tumor penetration than conventional paclitaxel therapy, investigators reported. The study is in the May issue of the Journal of Thoracic and Cardiovascular Surgery.

Dr. Hongyi Lei of Brigham and Women’s Hospital, Boston, and his colleagues used the in vitro mesothelioma spheroid model because two-dimensional in vitro monolayer cell culture experiments do not replicate the superior efficacy of paclitaxel-loaded expansile nanoparticles (Pax-eNPs), suggesting that Pax-eNPs utilize a unique drug delivery mechanism.

Courtesy of AATS

The study observed that spheroids treated with Pax-eNP showed increased drug penetration and a 38-fold higher intraspheroidal drug concentration at 24 hours than that of paclitaxel dissolved in Cremophor EL/ethanol (J. Thorac. Cardiovasc. Surg. 2014 [doi:10.1016/j.jtcvs.2015.02.020]).

The researchers said their findings showed that three-dimensional spheroid models “are valuable tools for investigating cytotoxic mechanisms and nanoparticle-tumor interactions, particularly given the costs and limitations of in vivo animal studies.” Their findings were first presented at the 94th Annual Meeting of the American Association of Thoracic Surgery last year in Toronto.

Despite advances of nanoparticle-based drug delivery systems, difficulties in evaluating the effectiveness of these drugs in local chemotherapy have hindered their adoption in the clinic. Studies of the same agent utilizing in vitro vs. in vivo methods have shown conflicting results.

The observation that Pax-eNP treatment of intraperitoneal mesothelioma significantly improved survival in lab animals in vivo compared to conventional paclitaxel led to the use of the three-dimensional spheroid model. Dr. Lei and colleagues called this revelation “striking” because Pax-eNP exposure of the identical mesothelioma tumor cells plated as a two-dimensional monolayer in vitro demonstrated equal or worse results. “This suggested that eNP may be more effective at penetration and/or persistence within multicellular tumors and led to the use of a 3-D tumor spheroid mode,” they said.

“Given the high cost and limitations of in vivo animal studies, spheroid models may present a clinically relevant platform for screening novel pharmaceuticals and unique drug-delivery systems during the preclinical phase,” the researchers indicated.

They also investigated spheroid cytotoxicity in a clinic-like setting following a 4-hour, high-dose (1,000 ng/mL) paclitaxel exposure via conventional and eNP vehicles. They found that Pax-eNP exposure led to greater tumor cytotoxicity at 72 hours, and that cytotoxicity continued seven days later because Pax-eNPs rapidly enter the tumor spheroid and remain intracellular, slowly releasing the drug.

“The prolonged drug release mechanism that pH-triggered Pax-eNP uses appears to be unique, leading to markedly higher intraspheroidal drug delivery, prolonged intratumoral drug release and superior antitumor efficacy,” the investigators concluded. The authors had no disclosures.

Malignant mesothelioma poses a significant challenge for clinicians because of its ability to resist chemotherapy, but the use of three-dimensional tumor spheroid models has shown that local administration of paclitaxel in a nanoparticle platform achieved better tumor penetration than conventional paclitaxel therapy, investigators reported. The study is in the May issue of the Journal of Thoracic and Cardiovascular Surgery.

Dr. Hongyi Lei of Brigham and Women’s Hospital, Boston, and his colleagues used the in vitro mesothelioma spheroid model because two-dimensional in vitro monolayer cell culture experiments do not replicate the superior efficacy of paclitaxel-loaded expansile nanoparticles (Pax-eNPs), suggesting that Pax-eNPs utilize a unique drug delivery mechanism.

Courtesy of AATS

The study observed that spheroids treated with Pax-eNP showed increased drug penetration and a 38-fold higher intraspheroidal drug concentration at 24 hours than that of paclitaxel dissolved in Cremophor EL/ethanol (J. Thorac. Cardiovasc. Surg. 2014 [doi:10.1016/j.jtcvs.2015.02.020]).

The researchers said their findings showed that three-dimensional spheroid models “are valuable tools for investigating cytotoxic mechanisms and nanoparticle-tumor interactions, particularly given the costs and limitations of in vivo animal studies.” Their findings were first presented at the 94th Annual Meeting of the American Association of Thoracic Surgery last year in Toronto.

Despite advances of nanoparticle-based drug delivery systems, difficulties in evaluating the effectiveness of these drugs in local chemotherapy have hindered their adoption in the clinic. Studies of the same agent utilizing in vitro vs. in vivo methods have shown conflicting results.

The observation that Pax-eNP treatment of intraperitoneal mesothelioma significantly improved survival in lab animals in vivo compared to conventional paclitaxel led to the use of the three-dimensional spheroid model. Dr. Lei and colleagues called this revelation “striking” because Pax-eNP exposure of the identical mesothelioma tumor cells plated as a two-dimensional monolayer in vitro demonstrated equal or worse results. “This suggested that eNP may be more effective at penetration and/or persistence within multicellular tumors and led to the use of a 3-D tumor spheroid mode,” they said.

“Given the high cost and limitations of in vivo animal studies, spheroid models may present a clinically relevant platform for screening novel pharmaceuticals and unique drug-delivery systems during the preclinical phase,” the researchers indicated.

They also investigated spheroid cytotoxicity in a clinic-like setting following a 4-hour, high-dose (1,000 ng/mL) paclitaxel exposure via conventional and eNP vehicles. They found that Pax-eNP exposure led to greater tumor cytotoxicity at 72 hours, and that cytotoxicity continued seven days later because Pax-eNPs rapidly enter the tumor spheroid and remain intracellular, slowly releasing the drug.

“The prolonged drug release mechanism that pH-triggered Pax-eNP uses appears to be unique, leading to markedly higher intraspheroidal drug delivery, prolonged intratumoral drug release and superior antitumor efficacy,” the investigators concluded. The authors had no disclosures.