Sharon Worcester

PHILADELPHIA– Long-term intake of meat and poultry is independently associated with an increased risk of developing hypertension, according to findings from an analysis of pooled data from three large prospective cohort studies.

The data also suggest that long-term intake of seafood does not protect against hypertension, Dr. Lea Borgi of Brigham and Women’s Hospital, Boston reported at Kidney Week 2014.

©camij/thinkstockphotos.com

Of approximately 122,000 women in the Nurses’ Health Study 1, 116,000 women in the Nurses’ Health Study II, and 52,000 men in the Health Professionals Follow-up Study, those with an intake of at least 1 serving daily of meat and poultry (processed meat, beef, lamb, chicken, or turkey) and those with at least 1 serving daily of meat, poultry and seafood (including canned tuna, dark meat fish, shrimp, and lobster) had a greater risk of hypertension than did those with an intake of less than 1 serving monthly (hazard ratios, 1.30 and 1.22, respectively), Dr. Borgi said.

Seafood alone was associated with an increased risk of hypertension in the Nurses’ Health Study 2 (hazard ratio 1.13) and in the Health Professionals Follow-Up Study (hazard ratio, 1.16).

“Now, given that the association of seafood with hypertension was unexpected, we did do a secondary analysis … and we actually were able to analyze different types of seafood such as canned tuna fish, dark meat fish, other fish, shrimp, lobster, or scallops,” she said.

Those who consumed 4-6 servings a week of canned tuna or dark meat fish had an increased risk of hypertension (hazard ratio, 1.13 and 1.24, respectively), she said.

Study subjects ranged in age from 27 to 75 years, and information about diet, behaviors, and health status was updated regularly in each of the studies. The subjects were followed for a mean of about 20 years.

The current analysis was adjusted for numerous hypertension risk factors, including known risk factors like age and body mass index, and factors shown to be associated with hypertension in the cohorts, including analgesia use and consumption of sugar-sweetened and artificially-sweetened beverages. Adjustment was also made for total consumption of fruits, vegetables, and grains, as decreased consumption of these foods may also be associated with hypertension. Random effects meta-analysis was used to derive pooled estimates of effect.

Prospective data on the relationship between red meat, seafood, and poultry consumption and hypertension are scarce, but red and processed meats are generally considered to have an adverse effect on cardiovascular health, while seafood is generally believed to be protective; the effect of poultry is controversial, as study results have been conflicting, Dr. Borgi said.

“Our finding that more meat intake was associated with increased risk of hypertension is broadly consistent with prior studies. We also found that a greater consumption of poultry was independently associated with increased hypertension risk, and we observed a weak increased risk of hypertension with increasing fish consumption overall,” she said, noting that the mechanisms for the relationship are “controversial and hypothetical,” and include a possible relationship between gut microflora and cardiovascular disease, which is supported by a growing body of evidence.

“One of these links is through the conversion of L-carnitine, which is highly found in red meat and salt water fish, to trimethylamine N-oxide (TMAO). Also, another potential mechanism is the production of Maillard reaction products (MRPs), which are chemical products that are formed when animal flesh is cooked at high temperatures,” she said, explaining that TMAO and MRPs are associated with increased oxidative stress and inflammation, which are important mechanisms in the development of hypertension.

Given the increasing prevalence of hypertension in the United States and around the world, the independent and significant association between higher intakes of meat, poultry, and seafood and greater risk of developing hypertension seen in this study has important public health implications, she said, adding that additional studies are needed to further assess the potential mechanisms underlying the association.

Dr. Borgi reported having no disclosures.

PHILADELPHIA– Long-term intake of meat and poultry is independently associated with an increased risk of developing hypertension, according to findings from an analysis of pooled data from three large prospective cohort studies.

The data also suggest that long-term intake of seafood does not protect against hypertension, Dr. Lea Borgi of Brigham and Women’s Hospital, Boston reported at Kidney Week 2014.

©camij/thinkstockphotos.com

Of approximately 122,000 women in the Nurses’ Health Study 1, 116,000 women in the Nurses’ Health Study II, and 52,000 men in the Health Professionals Follow-up Study, those with an intake of at least 1 serving daily of meat and poultry (processed meat, beef, lamb, chicken, or turkey) and those with at least 1 serving daily of meat, poultry and seafood (including canned tuna, dark meat fish, shrimp, and lobster) had a greater risk of hypertension than did those with an intake of less than 1 serving monthly (hazard ratios, 1.30 and 1.22, respectively), Dr. Borgi said.

Seafood alone was associated with an increased risk of hypertension in the Nurses’ Health Study 2 (hazard ratio 1.13) and in the Health Professionals Follow-Up Study (hazard ratio, 1.16).

“Now, given that the association of seafood with hypertension was unexpected, we did do a secondary analysis … and we actually were able to analyze different types of seafood such as canned tuna fish, dark meat fish, other fish, shrimp, lobster, or scallops,” she said.

Those who consumed 4-6 servings a week of canned tuna or dark meat fish had an increased risk of hypertension (hazard ratio, 1.13 and 1.24, respectively), she said.

Study subjects ranged in age from 27 to 75 years, and information about diet, behaviors, and health status was updated regularly in each of the studies. The subjects were followed for a mean of about 20 years.

The current analysis was adjusted for numerous hypertension risk factors, including known risk factors like age and body mass index, and factors shown to be associated with hypertension in the cohorts, including analgesia use and consumption of sugar-sweetened and artificially-sweetened beverages. Adjustment was also made for total consumption of fruits, vegetables, and grains, as decreased consumption of these foods may also be associated with hypertension. Random effects meta-analysis was used to derive pooled estimates of effect.

Prospective data on the relationship between red meat, seafood, and poultry consumption and hypertension are scarce, but red and processed meats are generally considered to have an adverse effect on cardiovascular health, while seafood is generally believed to be protective; the effect of poultry is controversial, as study results have been conflicting, Dr. Borgi said.

“Our finding that more meat intake was associated with increased risk of hypertension is broadly consistent with prior studies. We also found that a greater consumption of poultry was independently associated with increased hypertension risk, and we observed a weak increased risk of hypertension with increasing fish consumption overall,” she said, noting that the mechanisms for the relationship are “controversial and hypothetical,” and include a possible relationship between gut microflora and cardiovascular disease, which is supported by a growing body of evidence.

“One of these links is through the conversion of L-carnitine, which is highly found in red meat and salt water fish, to trimethylamine N-oxide (TMAO). Also, another potential mechanism is the production of Maillard reaction products (MRPs), which are chemical products that are formed when animal flesh is cooked at high temperatures,” she said, explaining that TMAO and MRPs are associated with increased oxidative stress and inflammation, which are important mechanisms in the development of hypertension.

Given the increasing prevalence of hypertension in the United States and around the world, the independent and significant association between higher intakes of meat, poultry, and seafood and greater risk of developing hypertension seen in this study has important public health implications, she said, adding that additional studies are needed to further assess the potential mechanisms underlying the association.

Dr. Borgi reported having no disclosures.

PHILADELPHIA– Long-term intake of meat and poultry is independently associated with an increased risk of developing hypertension, according to findings from an analysis of pooled data from three large prospective cohort studies.

The data also suggest that long-term intake of seafood does not protect against hypertension, Dr. Lea Borgi of Brigham and Women’s Hospital, Boston reported at Kidney Week 2014.

©camij/thinkstockphotos.com

Of approximately 122,000 women in the Nurses’ Health Study 1, 116,000 women in the Nurses’ Health Study II, and 52,000 men in the Health Professionals Follow-up Study, those with an intake of at least 1 serving daily of meat and poultry (processed meat, beef, lamb, chicken, or turkey) and those with at least 1 serving daily of meat, poultry and seafood (including canned tuna, dark meat fish, shrimp, and lobster) had a greater risk of hypertension than did those with an intake of less than 1 serving monthly (hazard ratios, 1.30 and 1.22, respectively), Dr. Borgi said.

Seafood alone was associated with an increased risk of hypertension in the Nurses’ Health Study 2 (hazard ratio 1.13) and in the Health Professionals Follow-Up Study (hazard ratio, 1.16).

“Now, given that the association of seafood with hypertension was unexpected, we did do a secondary analysis … and we actually were able to analyze different types of seafood such as canned tuna fish, dark meat fish, other fish, shrimp, lobster, or scallops,” she said.

Those who consumed 4-6 servings a week of canned tuna or dark meat fish had an increased risk of hypertension (hazard ratio, 1.13 and 1.24, respectively), she said.

Study subjects ranged in age from 27 to 75 years, and information about diet, behaviors, and health status was updated regularly in each of the studies. The subjects were followed for a mean of about 20 years.

The current analysis was adjusted for numerous hypertension risk factors, including known risk factors like age and body mass index, and factors shown to be associated with hypertension in the cohorts, including analgesia use and consumption of sugar-sweetened and artificially-sweetened beverages. Adjustment was also made for total consumption of fruits, vegetables, and grains, as decreased consumption of these foods may also be associated with hypertension. Random effects meta-analysis was used to derive pooled estimates of effect.

Prospective data on the relationship between red meat, seafood, and poultry consumption and hypertension are scarce, but red and processed meats are generally considered to have an adverse effect on cardiovascular health, while seafood is generally believed to be protective; the effect of poultry is controversial, as study results have been conflicting, Dr. Borgi said.

“Our finding that more meat intake was associated with increased risk of hypertension is broadly consistent with prior studies. We also found that a greater consumption of poultry was independently associated with increased hypertension risk, and we observed a weak increased risk of hypertension with increasing fish consumption overall,” she said, noting that the mechanisms for the relationship are “controversial and hypothetical,” and include a possible relationship between gut microflora and cardiovascular disease, which is supported by a growing body of evidence.

“One of these links is through the conversion of L-carnitine, which is highly found in red meat and salt water fish, to trimethylamine N-oxide (TMAO). Also, another potential mechanism is the production of Maillard reaction products (MRPs), which are chemical products that are formed when animal flesh is cooked at high temperatures,” she said, explaining that TMAO and MRPs are associated with increased oxidative stress and inflammation, which are important mechanisms in the development of hypertension.

Given the increasing prevalence of hypertension in the United States and around the world, the independent and significant association between higher intakes of meat, poultry, and seafood and greater risk of developing hypertension seen in this study has important public health implications, she said, adding that additional studies are needed to further assess the potential mechanisms underlying the association.

Dr. Borgi reported having no disclosures.

PHILADELPHIA – Children and young adults with increased systolic and diastolic indices and decreased nocturnal dipping on ambulatory blood pressure monitoring are at increased risk for cognitive dysfunction, according to findings from a cross-sectional study.

In 152 subjects aged 8-25 years, systolic index and diastolic indices – after controlling for chronic kidney disease (CKD) versus control group, race, and maternal education – were negatively associated with performance in several domains, including attention, inhibitory control, and verbal memory. For the attention domain, there was a 0.02 increase in z score for every 1% increase in diastolic dip. For the verbal memory and inhibitory control domains, there was a decrease of 0.14 and 0.06 in z score, respectively, for every 10% increase in diastolic load, Nina Laney of Children’s Hospital of Philadelphia reported.

Systolic dipping was negatively associated with set shifting, with a decrease of 0.03 in z score (P = .04) for every 1% decrease in systolic dipping.

“Hypertension is a well known risk factor for cognitive dysfunction in adults both with and without kidney disease. There are fewer studies that look at this in children, but those that have identify many of the same areas of dysfunction, including executive function, attention, memory, and verbal and visual skills,” Ms. Laney said at the meeting sponsored by the American Society of Nephrology.

The current findings suggest that hypertension affects cognitive function in younger patients, particularly given the decreased rate of comorbidities in children, compared with adults, and this has important implications for early detection and treatment, she said.

Study subjects were 96 patients with CKD and 56 healthy controls. Those with CKD had a mean age of 15.7 years and mean estimated glomerular filtration rate (eGFR) of 48.6 mL/min/1.73m². The healthy controls had a mean age of 15.1 years and mean eGFR of 103.1 mL/min/1.73m².

Each patient completed the ambulatory blood pressure measurement as well as a neurocognitive battery consisting of measures of language, attention, inhibitory control, problem solving, set shifting, visuospatial memory (verbal and visual), working memory (verbal and visual), and executive function.

Among the proposed mechanisms for the relationship between hypertension and cognitive dysfunction are impaired cerebral blood flow, autoregulation, decreased microvascular reactivity, and brain volume reduction in gray matter, she noted.

She noted, however, that the study is limited by relatively small sample size, the use of some assumptions while grouping tests into domains, and assessments only once for both the blood pressure and neuropositive assessments. Also, the results were not adjusted for multiple comparisons.

“For future analyses, we will use neuropositive results, blood pressure results, and neuroimaging to look at specific regions of interest in the brain and correlate them with performance in our neurocognitive testing,” she said.

This study was funded by the Pennsylvania Department of Health. Ms. Laney reported having no disclosures.

PHILADELPHIA – Children and young adults with increased systolic and diastolic indices and decreased nocturnal dipping on ambulatory blood pressure monitoring are at increased risk for cognitive dysfunction, according to findings from a cross-sectional study.

In 152 subjects aged 8-25 years, systolic index and diastolic indices – after controlling for chronic kidney disease (CKD) versus control group, race, and maternal education – were negatively associated with performance in several domains, including attention, inhibitory control, and verbal memory. For the attention domain, there was a 0.02 increase in z score for every 1% increase in diastolic dip. For the verbal memory and inhibitory control domains, there was a decrease of 0.14 and 0.06 in z score, respectively, for every 10% increase in diastolic load, Nina Laney of Children’s Hospital of Philadelphia reported.

Systolic dipping was negatively associated with set shifting, with a decrease of 0.03 in z score (P = .04) for every 1% decrease in systolic dipping.

“Hypertension is a well known risk factor for cognitive dysfunction in adults both with and without kidney disease. There are fewer studies that look at this in children, but those that have identify many of the same areas of dysfunction, including executive function, attention, memory, and verbal and visual skills,” Ms. Laney said at the meeting sponsored by the American Society of Nephrology.

The current findings suggest that hypertension affects cognitive function in younger patients, particularly given the decreased rate of comorbidities in children, compared with adults, and this has important implications for early detection and treatment, she said.

Study subjects were 96 patients with CKD and 56 healthy controls. Those with CKD had a mean age of 15.7 years and mean estimated glomerular filtration rate (eGFR) of 48.6 mL/min/1.73m². The healthy controls had a mean age of 15.1 years and mean eGFR of 103.1 mL/min/1.73m².

Each patient completed the ambulatory blood pressure measurement as well as a neurocognitive battery consisting of measures of language, attention, inhibitory control, problem solving, set shifting, visuospatial memory (verbal and visual), working memory (verbal and visual), and executive function.

Among the proposed mechanisms for the relationship between hypertension and cognitive dysfunction are impaired cerebral blood flow, autoregulation, decreased microvascular reactivity, and brain volume reduction in gray matter, she noted.

She noted, however, that the study is limited by relatively small sample size, the use of some assumptions while grouping tests into domains, and assessments only once for both the blood pressure and neuropositive assessments. Also, the results were not adjusted for multiple comparisons.

“For future analyses, we will use neuropositive results, blood pressure results, and neuroimaging to look at specific regions of interest in the brain and correlate them with performance in our neurocognitive testing,” she said.

This study was funded by the Pennsylvania Department of Health. Ms. Laney reported having no disclosures.

PHILADELPHIA – Children and young adults with increased systolic and diastolic indices and decreased nocturnal dipping on ambulatory blood pressure monitoring are at increased risk for cognitive dysfunction, according to findings from a cross-sectional study.

In 152 subjects aged 8-25 years, systolic index and diastolic indices – after controlling for chronic kidney disease (CKD) versus control group, race, and maternal education – were negatively associated with performance in several domains, including attention, inhibitory control, and verbal memory. For the attention domain, there was a 0.02 increase in z score for every 1% increase in diastolic dip. For the verbal memory and inhibitory control domains, there was a decrease of 0.14 and 0.06 in z score, respectively, for every 10% increase in diastolic load, Nina Laney of Children’s Hospital of Philadelphia reported.

Systolic dipping was negatively associated with set shifting, with a decrease of 0.03 in z score (P = .04) for every 1% decrease in systolic dipping.

“Hypertension is a well known risk factor for cognitive dysfunction in adults both with and without kidney disease. There are fewer studies that look at this in children, but those that have identify many of the same areas of dysfunction, including executive function, attention, memory, and verbal and visual skills,” Ms. Laney said at the meeting sponsored by the American Society of Nephrology.

The current findings suggest that hypertension affects cognitive function in younger patients, particularly given the decreased rate of comorbidities in children, compared with adults, and this has important implications for early detection and treatment, she said.

Study subjects were 96 patients with CKD and 56 healthy controls. Those with CKD had a mean age of 15.7 years and mean estimated glomerular filtration rate (eGFR) of 48.6 mL/min/1.73m². The healthy controls had a mean age of 15.1 years and mean eGFR of 103.1 mL/min/1.73m².

Each patient completed the ambulatory blood pressure measurement as well as a neurocognitive battery consisting of measures of language, attention, inhibitory control, problem solving, set shifting, visuospatial memory (verbal and visual), working memory (verbal and visual), and executive function.

Among the proposed mechanisms for the relationship between hypertension and cognitive dysfunction are impaired cerebral blood flow, autoregulation, decreased microvascular reactivity, and brain volume reduction in gray matter, she noted.

She noted, however, that the study is limited by relatively small sample size, the use of some assumptions while grouping tests into domains, and assessments only once for both the blood pressure and neuropositive assessments. Also, the results were not adjusted for multiple comparisons.

“For future analyses, we will use neuropositive results, blood pressure results, and neuroimaging to look at specific regions of interest in the brain and correlate them with performance in our neurocognitive testing,” she said.

This study was funded by the Pennsylvania Department of Health. Ms. Laney reported having no disclosures.

AUSTIN, TEX. – Ultrasound plus real-time transthoracic echocardiography sped up placements of central venous catheters and rule outs of insertion-related pneumothorax, compared with ultrasound alone in a prospective, randomized, controlled study of 60 patients in the medical intensive care unit of a single center.

Compared to conventional ultrasound placement with x-ray confirmation, ultrasound plus transthoracic echocardiography also reduced the time to approval of the line for use, Dr. Dileep Raman reported at the annual meeting of the American College of Chest Physicians.

Waiting for a chest x-ray adds anywhere from 16 minutes to 2 hours to the approval of line use, according to the literature. Ultrasound is “a cheap bedside tool that can be repeatedly used to reduce the amount of chest x-rays for line placement and insertion” and indeed reduced the need for chest x-ray to confirm central venous catheter (CVC) position – without adding to procedure time, he said.

In the study, ultrasound plus transthoracic echocardiography reduced the use of bedside chest x-rays by 57% in 30 patients, compared with conventional ultrasound placement with x-ray confirmation in 29 patients. The mean time to line use was 25 minutes in the ultrasound plus echo group and 53.6 minutes in the conventional placement group, said Dr. Raman of the Cleveland Clinic.

The mean time to complete the procedure was 24.1 minutes in the intervention group, compared with 27.7 minutes in the x-ray confirmation group, he said. None of the study patients had pneumothoraces.

Study subjects were consecutive patients admitted to an intensive care unit at a tertiary care medical center. Both the intervention and control groups had central venous catheters inserted under ultrasound guidance, but the intervention group underwent real-time transthoracic echocardiography to assist in catheter positioning, as well as chest ultrasonography to exclude a pneumothorax. After this process was completed, the line was immediately cleared for use. If the catheter wasn’t detected in the right atrium, the patient was switched to the control group, which was treated using conventional techniques followed by standard chest x-ray.

The study groups were well matched with respect to age, body mass index, and APACHE III score.

Obtaining a chest x-ray to confirm line placement and to exclude pneumothorax remains the standard of care in most ICUs, but Dr. Raman said he and his colleagues dispute that chest x-ray should remain the standard, as it doesn’t identify the superior vena cava–right atrium junction. Also, in addition to reducing the need for chest x-ray, the ultrasound technique seems to give a better picture of line placement.

Additional studies are needed to look at safety and feasibility, because pneumothorax rates are low, and “60 patients is clearly not enough to see if we dented the pneumothorax rate,” he said.

Dr. Raman reported having no disclosures.

AUSTIN, TEX. – Ultrasound plus real-time transthoracic echocardiography sped up placements of central venous catheters and rule outs of insertion-related pneumothorax, compared with ultrasound alone in a prospective, randomized, controlled study of 60 patients in the medical intensive care unit of a single center.

Compared to conventional ultrasound placement with x-ray confirmation, ultrasound plus transthoracic echocardiography also reduced the time to approval of the line for use, Dr. Dileep Raman reported at the annual meeting of the American College of Chest Physicians.

Waiting for a chest x-ray adds anywhere from 16 minutes to 2 hours to the approval of line use, according to the literature. Ultrasound is “a cheap bedside tool that can be repeatedly used to reduce the amount of chest x-rays for line placement and insertion” and indeed reduced the need for chest x-ray to confirm central venous catheter (CVC) position – without adding to procedure time, he said.

In the study, ultrasound plus transthoracic echocardiography reduced the use of bedside chest x-rays by 57% in 30 patients, compared with conventional ultrasound placement with x-ray confirmation in 29 patients. The mean time to line use was 25 minutes in the ultrasound plus echo group and 53.6 minutes in the conventional placement group, said Dr. Raman of the Cleveland Clinic.

The mean time to complete the procedure was 24.1 minutes in the intervention group, compared with 27.7 minutes in the x-ray confirmation group, he said. None of the study patients had pneumothoraces.

Study subjects were consecutive patients admitted to an intensive care unit at a tertiary care medical center. Both the intervention and control groups had central venous catheters inserted under ultrasound guidance, but the intervention group underwent real-time transthoracic echocardiography to assist in catheter positioning, as well as chest ultrasonography to exclude a pneumothorax. After this process was completed, the line was immediately cleared for use. If the catheter wasn’t detected in the right atrium, the patient was switched to the control group, which was treated using conventional techniques followed by standard chest x-ray.

The study groups were well matched with respect to age, body mass index, and APACHE III score.

Obtaining a chest x-ray to confirm line placement and to exclude pneumothorax remains the standard of care in most ICUs, but Dr. Raman said he and his colleagues dispute that chest x-ray should remain the standard, as it doesn’t identify the superior vena cava–right atrium junction. Also, in addition to reducing the need for chest x-ray, the ultrasound technique seems to give a better picture of line placement.

Additional studies are needed to look at safety and feasibility, because pneumothorax rates are low, and “60 patients is clearly not enough to see if we dented the pneumothorax rate,” he said.

Dr. Raman reported having no disclosures.

AUSTIN, TEX. – Ultrasound plus real-time transthoracic echocardiography sped up placements of central venous catheters and rule outs of insertion-related pneumothorax, compared with ultrasound alone in a prospective, randomized, controlled study of 60 patients in the medical intensive care unit of a single center.

Compared to conventional ultrasound placement with x-ray confirmation, ultrasound plus transthoracic echocardiography also reduced the time to approval of the line for use, Dr. Dileep Raman reported at the annual meeting of the American College of Chest Physicians.

Waiting for a chest x-ray adds anywhere from 16 minutes to 2 hours to the approval of line use, according to the literature. Ultrasound is “a cheap bedside tool that can be repeatedly used to reduce the amount of chest x-rays for line placement and insertion” and indeed reduced the need for chest x-ray to confirm central venous catheter (CVC) position – without adding to procedure time, he said.

In the study, ultrasound plus transthoracic echocardiography reduced the use of bedside chest x-rays by 57% in 30 patients, compared with conventional ultrasound placement with x-ray confirmation in 29 patients. The mean time to line use was 25 minutes in the ultrasound plus echo group and 53.6 minutes in the conventional placement group, said Dr. Raman of the Cleveland Clinic.

The mean time to complete the procedure was 24.1 minutes in the intervention group, compared with 27.7 minutes in the x-ray confirmation group, he said. None of the study patients had pneumothoraces.

Study subjects were consecutive patients admitted to an intensive care unit at a tertiary care medical center. Both the intervention and control groups had central venous catheters inserted under ultrasound guidance, but the intervention group underwent real-time transthoracic echocardiography to assist in catheter positioning, as well as chest ultrasonography to exclude a pneumothorax. After this process was completed, the line was immediately cleared for use. If the catheter wasn’t detected in the right atrium, the patient was switched to the control group, which was treated using conventional techniques followed by standard chest x-ray.

The study groups were well matched with respect to age, body mass index, and APACHE III score.

Obtaining a chest x-ray to confirm line placement and to exclude pneumothorax remains the standard of care in most ICUs, but Dr. Raman said he and his colleagues dispute that chest x-ray should remain the standard, as it doesn’t identify the superior vena cava–right atrium junction. Also, in addition to reducing the need for chest x-ray, the ultrasound technique seems to give a better picture of line placement.

Additional studies are needed to look at safety and feasibility, because pneumothorax rates are low, and “60 patients is clearly not enough to see if we dented the pneumothorax rate,” he said.

Dr. Raman reported having no disclosures.

AUSTIN, TEX. – Exacerbation rates were lower and lung function improved when patients with moderate or severe chronic obstructive pulmonary disease received combined treatment with the inhaled corticosteroid (ICS) budesonide and the long-acting beta₂-agonist (LABA) formoterol, as compared with patients who receive formoterol alone.

In a post hoc analysis of pooled data from three randomized double-blind studies, exacerbation rates were lower in the 197 patients with moderate airflow limitations and in the 975 patients with severe airflow limitations who received combination therapy, compared with the 211 and 963 patients, respectively, who received only formoterol.

The differences were seen regardless of whether antibiotics were used, regardless of airflow limitation severity, and despite an overall lower exacerbation rate in those with moderate vs. severe disease, Dr. Donald Tashkin reported at the annual meeting of the American College of Chest Physicians.

The lowest rate of exacerbations, 0.4 per patient-treatment-year, was among those in the combination therapy group who were not treated with antibiotics – suggesting infection was not a factor in the exacerbation. The exacerbation rate was 0.7 per patient-treatment-year in those with moderate airflow limitation who received only formoterol. The respective exacerbation rates in patients with severe airflow limitation were 0.8 for those who received combination therapy and 1.0 in those who received only formoterol. The corresponding rates for exacerbations among those who were additionally treated with antibiotics were 0.5 vs. 0.8 and 0.9 vs. 1.2, said Dr. Tashkin of the University of California, Los Angeles.

Further, an overall greater percentage of patients receiving combination therapy met responder criteria for at least a 100-mL improvement in predose forced expiratory volume in 1 second (FEV₁). The rates were 47% vs. 39% for combination vs. formoterol alone in patients with moderate airflow limitation, and 34% vs. 29%, respectively, in patients with severe airflow limitations, he said.

The pooled data for this analysis were from two 12-month trials and one 6-month trial of COPD patients aged 40 years or older with at least one COPD exacerbation in the past year. Two of the trials (the 12-month SUN study and the 6-month SHINE study) were pivotal randomized, placebo-controlled, double-blind, double-dummy trials that led to the approval of the budesonide/formoterol combination therapy, and the third was a non–placebo-controlled study, Dr. Tashkin noted.

Moderate disease was defined as FEV₁ percent predicted of at least 50%, and severe disease was defined as FEV₁ percent predicted of less than 50%. Exacerbations were defined as COPD worsening that required treatment with oral corticosteroids and/or hospitalization.

Combination therapy was administered twice daily via pressurized metered-dose inhaler at a dose of 320 mcg budesonide/9 mcg formoterol; formoterol-only therapy was administered twice daily via dry-powder inhaler at a dose of 9 mcg.

This study was supported by AstraZeneca. Dr. Tashkin reported receiving consulting fees and/or serving on a speakers bureau or advisory committee for AstraZeneca, Sunovion, Theravance, Pearl, Boehringer Ingelheim, and Forest, and receiving research funding or grant money from Sunovion, Pearl, and GlaxoSmithKline.

AUSTIN, TEX. – Exacerbation rates were lower and lung function improved when patients with moderate or severe chronic obstructive pulmonary disease received combined treatment with the inhaled corticosteroid (ICS) budesonide and the long-acting beta₂-agonist (LABA) formoterol, as compared with patients who receive formoterol alone.

In a post hoc analysis of pooled data from three randomized double-blind studies, exacerbation rates were lower in the 197 patients with moderate airflow limitations and in the 975 patients with severe airflow limitations who received combination therapy, compared with the 211 and 963 patients, respectively, who received only formoterol.

The differences were seen regardless of whether antibiotics were used, regardless of airflow limitation severity, and despite an overall lower exacerbation rate in those with moderate vs. severe disease, Dr. Donald Tashkin reported at the annual meeting of the American College of Chest Physicians.

The lowest rate of exacerbations, 0.4 per patient-treatment-year, was among those in the combination therapy group who were not treated with antibiotics – suggesting infection was not a factor in the exacerbation. The exacerbation rate was 0.7 per patient-treatment-year in those with moderate airflow limitation who received only formoterol. The respective exacerbation rates in patients with severe airflow limitation were 0.8 for those who received combination therapy and 1.0 in those who received only formoterol. The corresponding rates for exacerbations among those who were additionally treated with antibiotics were 0.5 vs. 0.8 and 0.9 vs. 1.2, said Dr. Tashkin of the University of California, Los Angeles.

Further, an overall greater percentage of patients receiving combination therapy met responder criteria for at least a 100-mL improvement in predose forced expiratory volume in 1 second (FEV₁). The rates were 47% vs. 39% for combination vs. formoterol alone in patients with moderate airflow limitation, and 34% vs. 29%, respectively, in patients with severe airflow limitations, he said.

The pooled data for this analysis were from two 12-month trials and one 6-month trial of COPD patients aged 40 years or older with at least one COPD exacerbation in the past year. Two of the trials (the 12-month SUN study and the 6-month SHINE study) were pivotal randomized, placebo-controlled, double-blind, double-dummy trials that led to the approval of the budesonide/formoterol combination therapy, and the third was a non–placebo-controlled study, Dr. Tashkin noted.

Moderate disease was defined as FEV₁ percent predicted of at least 50%, and severe disease was defined as FEV₁ percent predicted of less than 50%. Exacerbations were defined as COPD worsening that required treatment with oral corticosteroids and/or hospitalization.

Combination therapy was administered twice daily via pressurized metered-dose inhaler at a dose of 320 mcg budesonide/9 mcg formoterol; formoterol-only therapy was administered twice daily via dry-powder inhaler at a dose of 9 mcg.

This study was supported by AstraZeneca. Dr. Tashkin reported receiving consulting fees and/or serving on a speakers bureau or advisory committee for AstraZeneca, Sunovion, Theravance, Pearl, Boehringer Ingelheim, and Forest, and receiving research funding or grant money from Sunovion, Pearl, and GlaxoSmithKline.

AUSTIN, TEX. – Exacerbation rates were lower and lung function improved when patients with moderate or severe chronic obstructive pulmonary disease received combined treatment with the inhaled corticosteroid (ICS) budesonide and the long-acting beta₂-agonist (LABA) formoterol, as compared with patients who receive formoterol alone.

In a post hoc analysis of pooled data from three randomized double-blind studies, exacerbation rates were lower in the 197 patients with moderate airflow limitations and in the 975 patients with severe airflow limitations who received combination therapy, compared with the 211 and 963 patients, respectively, who received only formoterol.

The differences were seen regardless of whether antibiotics were used, regardless of airflow limitation severity, and despite an overall lower exacerbation rate in those with moderate vs. severe disease, Dr. Donald Tashkin reported at the annual meeting of the American College of Chest Physicians.

The lowest rate of exacerbations, 0.4 per patient-treatment-year, was among those in the combination therapy group who were not treated with antibiotics – suggesting infection was not a factor in the exacerbation. The exacerbation rate was 0.7 per patient-treatment-year in those with moderate airflow limitation who received only formoterol. The respective exacerbation rates in patients with severe airflow limitation were 0.8 for those who received combination therapy and 1.0 in those who received only formoterol. The corresponding rates for exacerbations among those who were additionally treated with antibiotics were 0.5 vs. 0.8 and 0.9 vs. 1.2, said Dr. Tashkin of the University of California, Los Angeles.

Further, an overall greater percentage of patients receiving combination therapy met responder criteria for at least a 100-mL improvement in predose forced expiratory volume in 1 second (FEV₁). The rates were 47% vs. 39% for combination vs. formoterol alone in patients with moderate airflow limitation, and 34% vs. 29%, respectively, in patients with severe airflow limitations, he said.

The pooled data for this analysis were from two 12-month trials and one 6-month trial of COPD patients aged 40 years or older with at least one COPD exacerbation in the past year. Two of the trials (the 12-month SUN study and the 6-month SHINE study) were pivotal randomized, placebo-controlled, double-blind, double-dummy trials that led to the approval of the budesonide/formoterol combination therapy, and the third was a non–placebo-controlled study, Dr. Tashkin noted.

Moderate disease was defined as FEV₁ percent predicted of at least 50%, and severe disease was defined as FEV₁ percent predicted of less than 50%. Exacerbations were defined as COPD worsening that required treatment with oral corticosteroids and/or hospitalization.

Combination therapy was administered twice daily via pressurized metered-dose inhaler at a dose of 320 mcg budesonide/9 mcg formoterol; formoterol-only therapy was administered twice daily via dry-powder inhaler at a dose of 9 mcg.

This study was supported by AstraZeneca. Dr. Tashkin reported receiving consulting fees and/or serving on a speakers bureau or advisory committee for AstraZeneca, Sunovion, Theravance, Pearl, Boehringer Ingelheim, and Forest, and receiving research funding or grant money from Sunovion, Pearl, and GlaxoSmithKline.

AUSTIN, TEX. – Obstructive sleep apnea appeared to provide protection against in-hospital mortality and nonroutine discharge among mechanically ventilated patients with pneumonia who were included in the National Inpatient Sample from 2009 to 2011.

Patients included in the analysis were 20,652 adults with a mean age of 65 years who were hospitalized with a primary diagnosis of pneumonia requiring invasive mechanical ventilation, representing nearly 107,000 such discharges nationally. About 8% of the patients had obstructive sleep apnea (OSA), and 11% were obese. Overall mortality was 31%, and the overall rate of nonroutine discharge, defined as discharge to a skilled nursing facility or to home with home health care, was 84%, Dr. Charlisa Gibson reported at the annual meeting of the American College of Chest Physicians.

Though limited by its retrospective nature and possible underreporting of OSA, this study demonstrates that OSA in patients with pneumonia requiring invasive mechanical ventilation confers a survival benefit, she said.

Those with OSA had a significantly higher rate of tracheostomy (9.2% vs. 8.3%), a lower rate of in-hospital mortality (19% vs. 31%), and a lower rate of nonroutine discharge (77% vs. 84%), compared with non-OSA patients. Length of stay was about 14 days in both groups, said Dr. Gibson, of Mount Sinai St. Luke’s-Roosevelt Hospital, New York.

Those in the non-OSA group had higher rates of shock and septicemia.

After adjustment for age, sex, obesity, comorbidities, and disease severity, OSA was a significant predictor of decreased in-hospital mortality (odds ratio, 0.74) and nonroutine discharge (odds ratio, 0.73), Dr. Gibson said.

“In pretty much all of the conditions of interest we looked at, we consistently saw that mortality was lower in the OSA group, whether they were obese or not … and whether or not they were deemed to have a low, moderate, or severe [Charlson Comorbidity Index],” she said.

OSA is an important and likely underdiagnosed comorbidity in hospitalized patients, and pneumonia remains a significant infectious cause of morbidity and mortality in hospitalized patients, she said. OSA affects about 5%-24% of the general population, but the percentage of hospitalized patients with OSA is uncertain.

About 20% of hospitalized patients with pneumonia end up in the intensive care unit for supportive treatment with mechanical ventilation.

“Once they are vented, there are data to suggest that early tracheostomy may shorten time on mechanical ventilation and hospital length of stay, but whether or not there’s an actual impact on mortality is controversial,” she said.

While prospective randomized controlled studies are needed to better identify risk factors for mortality, Dr. Gibson said there are several possible explanations for the findings of a protective effect of OSA in hospitalized patients with acute respiratory failure due to pneumonia.

First, non-OSA patients had more septicemia and shock, which suggests they may have had multisystem organ failure and required treatments like renal replacement therapy that independently increased their risk of mortality.

Also, the increased incidence of tracheostomy in the OSA patients may indicate that clinicians were more aggressive in treating patients with OSA, and that those patients may have benefited from earlier tracheostomy, she said.

There is some evidence to suggest that OSA patients have additional coronary collateral circulation, which means that they may have less severe cardiac injury because of this adaptation, and thus may have a lower risk of experiencing a fatal heart attack, compared with non-OSA patients, she explained.

The “obesity paradox” might also work in OSA patients’ favor, she said. There is some evidence that obese patients have increased metabolic reserve that results in lower complication rates, compared with normal weight patients.

“However, we do recommend that regardless of what the reason is, when these patients do come to the unit we should be aggressive and treat them with invasive mechanical ventilation if needed,” she said.

Dr. Gibson reported having no disclosures.

AUSTIN, TEX. – Obstructive sleep apnea appeared to provide protection against in-hospital mortality and nonroutine discharge among mechanically ventilated patients with pneumonia who were included in the National Inpatient Sample from 2009 to 2011.

Patients included in the analysis were 20,652 adults with a mean age of 65 years who were hospitalized with a primary diagnosis of pneumonia requiring invasive mechanical ventilation, representing nearly 107,000 such discharges nationally. About 8% of the patients had obstructive sleep apnea (OSA), and 11% were obese. Overall mortality was 31%, and the overall rate of nonroutine discharge, defined as discharge to a skilled nursing facility or to home with home health care, was 84%, Dr. Charlisa Gibson reported at the annual meeting of the American College of Chest Physicians.

Though limited by its retrospective nature and possible underreporting of OSA, this study demonstrates that OSA in patients with pneumonia requiring invasive mechanical ventilation confers a survival benefit, she said.

Those with OSA had a significantly higher rate of tracheostomy (9.2% vs. 8.3%), a lower rate of in-hospital mortality (19% vs. 31%), and a lower rate of nonroutine discharge (77% vs. 84%), compared with non-OSA patients. Length of stay was about 14 days in both groups, said Dr. Gibson, of Mount Sinai St. Luke’s-Roosevelt Hospital, New York.

Those in the non-OSA group had higher rates of shock and septicemia.

After adjustment for age, sex, obesity, comorbidities, and disease severity, OSA was a significant predictor of decreased in-hospital mortality (odds ratio, 0.74) and nonroutine discharge (odds ratio, 0.73), Dr. Gibson said.

“In pretty much all of the conditions of interest we looked at, we consistently saw that mortality was lower in the OSA group, whether they were obese or not … and whether or not they were deemed to have a low, moderate, or severe [Charlson Comorbidity Index],” she said.

OSA is an important and likely underdiagnosed comorbidity in hospitalized patients, and pneumonia remains a significant infectious cause of morbidity and mortality in hospitalized patients, she said. OSA affects about 5%-24% of the general population, but the percentage of hospitalized patients with OSA is uncertain.

About 20% of hospitalized patients with pneumonia end up in the intensive care unit for supportive treatment with mechanical ventilation.

“Once they are vented, there are data to suggest that early tracheostomy may shorten time on mechanical ventilation and hospital length of stay, but whether or not there’s an actual impact on mortality is controversial,” she said.

While prospective randomized controlled studies are needed to better identify risk factors for mortality, Dr. Gibson said there are several possible explanations for the findings of a protective effect of OSA in hospitalized patients with acute respiratory failure due to pneumonia.

First, non-OSA patients had more septicemia and shock, which suggests they may have had multisystem organ failure and required treatments like renal replacement therapy that independently increased their risk of mortality.

Also, the increased incidence of tracheostomy in the OSA patients may indicate that clinicians were more aggressive in treating patients with OSA, and that those patients may have benefited from earlier tracheostomy, she said.

There is some evidence to suggest that OSA patients have additional coronary collateral circulation, which means that they may have less severe cardiac injury because of this adaptation, and thus may have a lower risk of experiencing a fatal heart attack, compared with non-OSA patients, she explained.

The “obesity paradox” might also work in OSA patients’ favor, she said. There is some evidence that obese patients have increased metabolic reserve that results in lower complication rates, compared with normal weight patients.

“However, we do recommend that regardless of what the reason is, when these patients do come to the unit we should be aggressive and treat them with invasive mechanical ventilation if needed,” she said.

Dr. Gibson reported having no disclosures.

AUSTIN, TEX. – Obstructive sleep apnea appeared to provide protection against in-hospital mortality and nonroutine discharge among mechanically ventilated patients with pneumonia who were included in the National Inpatient Sample from 2009 to 2011.

Patients included in the analysis were 20,652 adults with a mean age of 65 years who were hospitalized with a primary diagnosis of pneumonia requiring invasive mechanical ventilation, representing nearly 107,000 such discharges nationally. About 8% of the patients had obstructive sleep apnea (OSA), and 11% were obese. Overall mortality was 31%, and the overall rate of nonroutine discharge, defined as discharge to a skilled nursing facility or to home with home health care, was 84%, Dr. Charlisa Gibson reported at the annual meeting of the American College of Chest Physicians.

Though limited by its retrospective nature and possible underreporting of OSA, this study demonstrates that OSA in patients with pneumonia requiring invasive mechanical ventilation confers a survival benefit, she said.

Those with OSA had a significantly higher rate of tracheostomy (9.2% vs. 8.3%), a lower rate of in-hospital mortality (19% vs. 31%), and a lower rate of nonroutine discharge (77% vs. 84%), compared with non-OSA patients. Length of stay was about 14 days in both groups, said Dr. Gibson, of Mount Sinai St. Luke’s-Roosevelt Hospital, New York.

Those in the non-OSA group had higher rates of shock and septicemia.

After adjustment for age, sex, obesity, comorbidities, and disease severity, OSA was a significant predictor of decreased in-hospital mortality (odds ratio, 0.74) and nonroutine discharge (odds ratio, 0.73), Dr. Gibson said.

“In pretty much all of the conditions of interest we looked at, we consistently saw that mortality was lower in the OSA group, whether they were obese or not … and whether or not they were deemed to have a low, moderate, or severe [Charlson Comorbidity Index],” she said.

OSA is an important and likely underdiagnosed comorbidity in hospitalized patients, and pneumonia remains a significant infectious cause of morbidity and mortality in hospitalized patients, she said. OSA affects about 5%-24% of the general population, but the percentage of hospitalized patients with OSA is uncertain.

About 20% of hospitalized patients with pneumonia end up in the intensive care unit for supportive treatment with mechanical ventilation.

“Once they are vented, there are data to suggest that early tracheostomy may shorten time on mechanical ventilation and hospital length of stay, but whether or not there’s an actual impact on mortality is controversial,” she said.

While prospective randomized controlled studies are needed to better identify risk factors for mortality, Dr. Gibson said there are several possible explanations for the findings of a protective effect of OSA in hospitalized patients with acute respiratory failure due to pneumonia.

First, non-OSA patients had more septicemia and shock, which suggests they may have had multisystem organ failure and required treatments like renal replacement therapy that independently increased their risk of mortality.

Also, the increased incidence of tracheostomy in the OSA patients may indicate that clinicians were more aggressive in treating patients with OSA, and that those patients may have benefited from earlier tracheostomy, she said.

There is some evidence to suggest that OSA patients have additional coronary collateral circulation, which means that they may have less severe cardiac injury because of this adaptation, and thus may have a lower risk of experiencing a fatal heart attack, compared with non-OSA patients, she explained.

The “obesity paradox” might also work in OSA patients’ favor, she said. There is some evidence that obese patients have increased metabolic reserve that results in lower complication rates, compared with normal weight patients.

“However, we do recommend that regardless of what the reason is, when these patients do come to the unit we should be aggressive and treat them with invasive mechanical ventilation if needed,” she said.

Dr. Gibson reported having no disclosures.

AUSTIN, TEX. – Adding a long-acting beta₂-agonist to long-acting muscarinic antagonist therapy in patients with low- or moderate-complexity chronic obstructive pulmonary disease appeared to increase costs without providing significant benefit, according to findings from a retrospective cohort study.

The mean all-cause drug-related cost was $5,808 among 274 patients who received LAMA/LABA combination therapy between Jan. 1, 2009, and March 31, 2012, according to the MarketScan database, compared with $7,902 among 1,370 patients receiving LAMA monotherapy, Mona Khalid of Epstein Health, New York, reported at the annual meeting of the American College of Chest Physicians.

After adjustment for observed differences in baseline characteristics, such as disease complexity and comorbidities as assessed by Charlson comorbidity index score, the combination and monotherapy patients had similar all-cause health care resource utilization, with comparable rates of inpatient visits, office visits, and emergency department visits.

“Where we did see some difference was in COPD-related office visits. The patients on combination therapy were twice as likely to have an office visit,” Ms. Khalid said, noting that this difference between groups was statistically significant, and resulted in a mean of $92 more in costs in the combination therapy group.

The overall drug-related costs after adjustment were $1,003 higher in the combination therapy group, she said.

As for treatment adherence, 17% of patients in the combination therapy group had 80% or more days covered with therapy, compared with 25% of those in the monotherapy group. The medication possession ratio was 41% in the combination group, compared with 46% in the monotherapy group (adjusted difference about 5%).

The combination therapy patients included all patients receiving LAMA/LABA therapy identified in the database – which includes commercially insured patients and Medicare patients with supplemental coverage through an employer – during the study period. All were older than 40 years, had medical and pharmacy claims data available for at least 1 year before and after the index date, and had at least one COPD-related claim – but no claims for asthma, nonspecified bronchitis, respiratory cancer, cystic fibrosis, or LABA or LAMA use within the past year. LAMA patients were randomly selected using those same criteria and matched in a 5:1 ratio.

Most of the patients had low-complexity or moderate-complexity disease, although a few patients had severe disease, Ms. Khalid noted.

Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines call for the use of LAMA monotherapy early in the course of COPD among patients with low to moderate disease complexity. Some patients, however, initiate combination therapy during that phase of disease. The findings support the GOLD monotherapy recommendation in these patients, Ms. Khalid said, although they are limited by factors associated with the retrospective study design and an inability to control well for disease severity because of the use of “claims history as proxy.”

The study was conducted prior to approval of the single-inhaler LABA/LAMA combination therapy, she cautioned, so the results can’t necessarily be extended to that therapy. In addition, because of the use of the MarketScan database, the study findings can’t necessarily be extended to the uninsured population or the Medicaid population, Ms. Khalid noted.

The study was funded by Forest Laboratories. Ms. Khalid’s employer, Epstein Health, received consulting fees from Forest to conduct the study.

AUSTIN, TEX. – Adding a long-acting beta₂-agonist to long-acting muscarinic antagonist therapy in patients with low- or moderate-complexity chronic obstructive pulmonary disease appeared to increase costs without providing significant benefit, according to findings from a retrospective cohort study.

The mean all-cause drug-related cost was $5,808 among 274 patients who received LAMA/LABA combination therapy between Jan. 1, 2009, and March 31, 2012, according to the MarketScan database, compared with $7,902 among 1,370 patients receiving LAMA monotherapy, Mona Khalid of Epstein Health, New York, reported at the annual meeting of the American College of Chest Physicians.

After adjustment for observed differences in baseline characteristics, such as disease complexity and comorbidities as assessed by Charlson comorbidity index score, the combination and monotherapy patients had similar all-cause health care resource utilization, with comparable rates of inpatient visits, office visits, and emergency department visits.

“Where we did see some difference was in COPD-related office visits. The patients on combination therapy were twice as likely to have an office visit,” Ms. Khalid said, noting that this difference between groups was statistically significant, and resulted in a mean of $92 more in costs in the combination therapy group.

The overall drug-related costs after adjustment were $1,003 higher in the combination therapy group, she said.

As for treatment adherence, 17% of patients in the combination therapy group had 80% or more days covered with therapy, compared with 25% of those in the monotherapy group. The medication possession ratio was 41% in the combination group, compared with 46% in the monotherapy group (adjusted difference about 5%).

The combination therapy patients included all patients receiving LAMA/LABA therapy identified in the database – which includes commercially insured patients and Medicare patients with supplemental coverage through an employer – during the study period. All were older than 40 years, had medical and pharmacy claims data available for at least 1 year before and after the index date, and had at least one COPD-related claim – but no claims for asthma, nonspecified bronchitis, respiratory cancer, cystic fibrosis, or LABA or LAMA use within the past year. LAMA patients were randomly selected using those same criteria and matched in a 5:1 ratio.

Most of the patients had low-complexity or moderate-complexity disease, although a few patients had severe disease, Ms. Khalid noted.

Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines call for the use of LAMA monotherapy early in the course of COPD among patients with low to moderate disease complexity. Some patients, however, initiate combination therapy during that phase of disease. The findings support the GOLD monotherapy recommendation in these patients, Ms. Khalid said, although they are limited by factors associated with the retrospective study design and an inability to control well for disease severity because of the use of “claims history as proxy.”

The study was conducted prior to approval of the single-inhaler LABA/LAMA combination therapy, she cautioned, so the results can’t necessarily be extended to that therapy. In addition, because of the use of the MarketScan database, the study findings can’t necessarily be extended to the uninsured population or the Medicaid population, Ms. Khalid noted.

The study was funded by Forest Laboratories. Ms. Khalid’s employer, Epstein Health, received consulting fees from Forest to conduct the study.

AUSTIN, TEX. – Adding a long-acting beta₂-agonist to long-acting muscarinic antagonist therapy in patients with low- or moderate-complexity chronic obstructive pulmonary disease appeared to increase costs without providing significant benefit, according to findings from a retrospective cohort study.

The mean all-cause drug-related cost was $5,808 among 274 patients who received LAMA/LABA combination therapy between Jan. 1, 2009, and March 31, 2012, according to the MarketScan database, compared with $7,902 among 1,370 patients receiving LAMA monotherapy, Mona Khalid of Epstein Health, New York, reported at the annual meeting of the American College of Chest Physicians.

After adjustment for observed differences in baseline characteristics, such as disease complexity and comorbidities as assessed by Charlson comorbidity index score, the combination and monotherapy patients had similar all-cause health care resource utilization, with comparable rates of inpatient visits, office visits, and emergency department visits.

“Where we did see some difference was in COPD-related office visits. The patients on combination therapy were twice as likely to have an office visit,” Ms. Khalid said, noting that this difference between groups was statistically significant, and resulted in a mean of $92 more in costs in the combination therapy group.

The overall drug-related costs after adjustment were $1,003 higher in the combination therapy group, she said.

As for treatment adherence, 17% of patients in the combination therapy group had 80% or more days covered with therapy, compared with 25% of those in the monotherapy group. The medication possession ratio was 41% in the combination group, compared with 46% in the monotherapy group (adjusted difference about 5%).

The combination therapy patients included all patients receiving LAMA/LABA therapy identified in the database – which includes commercially insured patients and Medicare patients with supplemental coverage through an employer – during the study period. All were older than 40 years, had medical and pharmacy claims data available for at least 1 year before and after the index date, and had at least one COPD-related claim – but no claims for asthma, nonspecified bronchitis, respiratory cancer, cystic fibrosis, or LABA or LAMA use within the past year. LAMA patients were randomly selected using those same criteria and matched in a 5:1 ratio.

Most of the patients had low-complexity or moderate-complexity disease, although a few patients had severe disease, Ms. Khalid noted.

Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines call for the use of LAMA monotherapy early in the course of COPD among patients with low to moderate disease complexity. Some patients, however, initiate combination therapy during that phase of disease. The findings support the GOLD monotherapy recommendation in these patients, Ms. Khalid said, although they are limited by factors associated with the retrospective study design and an inability to control well for disease severity because of the use of “claims history as proxy.”

The study was conducted prior to approval of the single-inhaler LABA/LAMA combination therapy, she cautioned, so the results can’t necessarily be extended to that therapy. In addition, because of the use of the MarketScan database, the study findings can’t necessarily be extended to the uninsured population or the Medicaid population, Ms. Khalid noted.

The study was funded by Forest Laboratories. Ms. Khalid’s employer, Epstein Health, received consulting fees from Forest to conduct the study.

AUSTIN, TEX. – A quality improvement initiative reduced the number of days on a urinary catheter and improved catheter utilization among patients in a chronic ventilator-dependent unit.

During a preintervention period, 24 of 37 patients (65%) were catheterized for a total of 107 urinary catheter days (mean of 4.5 per patient); after the 2-month intervention that relied on a standardized electronic checklist and visual reminders, 18 of 35 patients (51%) were catheterized for a total of 58 urinary catheter days (mean of 3.2 per patient). Further, the device utilization ratio decreased from 0.299 before the intervention to 0.212 after, Dr. Perliveh Carrera reported at the annual meeting of the American College of Chest Physicians.

The catheter utilization rates on the unit were below the national average of 0.45, and the rates of catheter-associated urinary tract infections (CAUTI) were relatively low. The unit’s rates had increased in 2012 and 2013, however, prompting this effort to reduce infections by reducing utilization.

“CAUTI is the most common health care–associated infection, affecting up to 20% of patients,” said Dr. Carrera of the Mayo Clinic in Rochester, Minn.

About 80% of CAUTIs are precipitated by an indwelling catheter, and up to half of catheterized patients don’t have an indication for catheter placement, she said. Data suggest that 20%-50% of catheters are inappropriately placed, and catheter placement is an important modifiable risk factor for preventing UTI.

The quality initiative was implemented on a nine-bed chronic ventilator unit where adult patients had an average length of stay of about 2 weeks. The intervention involved the use of a Define, Measure, Analyze, Improve, and Control (DMAIC) framework and included a combination of multidisciplinary teamwork and tools for promoting adherence. These tools included educational presentations to staff, posters, reminder cards on patients’ doors, and promotion of an electronic checklist that required input of an appropriate indication for catheterization. A charge nurse was provided with a portable tablet to track use of the electronic checklist.

The approach was developed after an initial survey of nursing staff identified low utilization of a paper checklist and knowledge gaps about catheter utilization and infection control efforts, Dr. Carrera said.

The initiative was associated with a significant increase in electronic checklist compliance – from 33% to 79% – and with a trend toward a reduction in the number of urinary catheter days and catheter utilization, she said.

As a quality metric, catheter days and utilization are more stable than CAUTI, which has been recognized as labile and subject to wide variation, she added.

Dr. Carrera reported having no disclosures.

AUSTIN, TEX. – A quality improvement initiative reduced the number of days on a urinary catheter and improved catheter utilization among patients in a chronic ventilator-dependent unit.

During a preintervention period, 24 of 37 patients (65%) were catheterized for a total of 107 urinary catheter days (mean of 4.5 per patient); after the 2-month intervention that relied on a standardized electronic checklist and visual reminders, 18 of 35 patients (51%) were catheterized for a total of 58 urinary catheter days (mean of 3.2 per patient). Further, the device utilization ratio decreased from 0.299 before the intervention to 0.212 after, Dr. Perliveh Carrera reported at the annual meeting of the American College of Chest Physicians.

The catheter utilization rates on the unit were below the national average of 0.45, and the rates of catheter-associated urinary tract infections (CAUTI) were relatively low. The unit’s rates had increased in 2012 and 2013, however, prompting this effort to reduce infections by reducing utilization.

“CAUTI is the most common health care–associated infection, affecting up to 20% of patients,” said Dr. Carrera of the Mayo Clinic in Rochester, Minn.

About 80% of CAUTIs are precipitated by an indwelling catheter, and up to half of catheterized patients don’t have an indication for catheter placement, she said. Data suggest that 20%-50% of catheters are inappropriately placed, and catheter placement is an important modifiable risk factor for preventing UTI.

The quality initiative was implemented on a nine-bed chronic ventilator unit where adult patients had an average length of stay of about 2 weeks. The intervention involved the use of a Define, Measure, Analyze, Improve, and Control (DMAIC) framework and included a combination of multidisciplinary teamwork and tools for promoting adherence. These tools included educational presentations to staff, posters, reminder cards on patients’ doors, and promotion of an electronic checklist that required input of an appropriate indication for catheterization. A charge nurse was provided with a portable tablet to track use of the electronic checklist.

The approach was developed after an initial survey of nursing staff identified low utilization of a paper checklist and knowledge gaps about catheter utilization and infection control efforts, Dr. Carrera said.

The initiative was associated with a significant increase in electronic checklist compliance – from 33% to 79% – and with a trend toward a reduction in the number of urinary catheter days and catheter utilization, she said.

As a quality metric, catheter days and utilization are more stable than CAUTI, which has been recognized as labile and subject to wide variation, she added.

Dr. Carrera reported having no disclosures.

AUSTIN, TEX. – A quality improvement initiative reduced the number of days on a urinary catheter and improved catheter utilization among patients in a chronic ventilator-dependent unit.

During a preintervention period, 24 of 37 patients (65%) were catheterized for a total of 107 urinary catheter days (mean of 4.5 per patient); after the 2-month intervention that relied on a standardized electronic checklist and visual reminders, 18 of 35 patients (51%) were catheterized for a total of 58 urinary catheter days (mean of 3.2 per patient). Further, the device utilization ratio decreased from 0.299 before the intervention to 0.212 after, Dr. Perliveh Carrera reported at the annual meeting of the American College of Chest Physicians.

The catheter utilization rates on the unit were below the national average of 0.45, and the rates of catheter-associated urinary tract infections (CAUTI) were relatively low. The unit’s rates had increased in 2012 and 2013, however, prompting this effort to reduce infections by reducing utilization.

“CAUTI is the most common health care–associated infection, affecting up to 20% of patients,” said Dr. Carrera of the Mayo Clinic in Rochester, Minn.

About 80% of CAUTIs are precipitated by an indwelling catheter, and up to half of catheterized patients don’t have an indication for catheter placement, she said. Data suggest that 20%-50% of catheters are inappropriately placed, and catheter placement is an important modifiable risk factor for preventing UTI.

The quality initiative was implemented on a nine-bed chronic ventilator unit where adult patients had an average length of stay of about 2 weeks. The intervention involved the use of a Define, Measure, Analyze, Improve, and Control (DMAIC) framework and included a combination of multidisciplinary teamwork and tools for promoting adherence. These tools included educational presentations to staff, posters, reminder cards on patients’ doors, and promotion of an electronic checklist that required input of an appropriate indication for catheterization. A charge nurse was provided with a portable tablet to track use of the electronic checklist.

The approach was developed after an initial survey of nursing staff identified low utilization of a paper checklist and knowledge gaps about catheter utilization and infection control efforts, Dr. Carrera said.

The initiative was associated with a significant increase in electronic checklist compliance – from 33% to 79% – and with a trend toward a reduction in the number of urinary catheter days and catheter utilization, she said.

As a quality metric, catheter days and utilization are more stable than CAUTI, which has been recognized as labile and subject to wide variation, she added.

Dr. Carrera reported having no disclosures.

PHILADELPHIA – Brincidofovir, an orally available lipid conjugate of cidofovir, appears promising for the treatment of adenovirus infection in children and young adults, according to findings from the open-label pilot portion of a phase III study.

Of 26 patients from birth through age 29 years who were enrolled in the study as of July 15, 13 discontinued treatment prematurely, 4 completed treatment, and 9 continued with treatment. Plasma viral load decreased over time in most of the 13 patients who either completed or remained on treatment, Dr. Jo-Anne Young reported at an annual scientific meeting on infectious diseases.

After a median treatment duration of 54 days, clearance of adenovirus from respiratory secretions, urine, and stool among those patients in whom these values were measured at baseline was 42%, 33%, and 27%, respectively. Mortality was 46% among all 26 patients and was 38% among patients with disseminated disease. In a prior expanded-access trial of the drug, mortality was 51% in treated patients with disseminated disease, and in a historical cohort from a 2003 study of patients with disseminated disease, mortality at 1 year was 82%.

Of note, one patient in the current study experienced an increase in viral load; that patient had received prior treatment with brincidofovir, and was found to have a T87I mutation with known resistance to cidofovir and brincidofovir. Six other patients with prior cidofovir exposure reached undetectable levels of adenovirus, and one had a greater than 2-log decline, so the effect of prior exposure on treatment response remains uncertain, Dr. Young of the University of Minnesota Medical Center, Minneapolis, said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Another trend that was noted in the current study was a possible increase in viral load prior to a decline in viral load. In one case this occurred in association with treatment interruption due to moderate hyperbilirubinemia, but the viral load declined again once treatment was restarted, and was undetectable by the 8th week of treatment.

Most of the patients in the study to date (80%) were children, 65% were males, 65% were white, and 65% had disseminated infection with two or more body systems affected. Most of those were high-risk patients, who had received hematopoietic stem cell transplants from unrelated donors, Dr. Young noted.

Half of the patients had a high viral copy load in their blood, and many had multiple viruses detected. For example, 27% had BK virus in their urine, 19% had cytomegalovirus detected in their plasma, and 8% had Epstein-Barr virus detected in their plasma .

Treatment was given as a twice-weekly 100-mg dose in adults weighing at least 50 kg, and as a twice-weekly, 2-mg/kg dose in children under age 12 or weighing less than 50 kg. Treatment duration was 12 weeks, and patients were followed for an additional 24 weeks.

Of the 13 patients who discontinued treatment, 4 died, 3 discontinued because of an adverse event (including 2 cases of diarrhea considered treatment related and 1 case of liver function testing abnormalities deemed unrelated to treatment), 2 discontinued on physician advice, 2 started other therapy, 1 experienced progression of transplant qualifying disease, and 1 withdrew consent for study participation. Among those who continued, median treatment duration was 54 days at the time the data were presented.

“Adenovirus is an infection with a high unmet medical treatment need,” Dr. Young said, noting that it is associated with a wide spectrum of disease, ranging from asymptomatic viremia to disseminated disease, particularly among hematopoietic stem cell transplant recipients.

The reported incidence varies from 5% to 50%, and mortality ranges from 26% for untreated symptomatic infection to 80% for disseminated disease.

Risk factors include pediatric age, high-risk types of allogeneic transplants, and the presence of acute graft vs. host disease in any transplant recipient.

Current treatment strategies involve supportive care with a reduction in immune suppression and/or initiation of direct antiviral treatment – typically intravenous cidofovir, which is associated with a risk of significant renal injury, Dr. Young said.

Brincidofovir, however, allows for oral dosing and high intracellular uptake, delivering high intracellular levels of the active antiviral, she noted, adding that there is no evidence of nephrotoxicity or hematologic toxicity associated with brincidofovir.

Antiadenovirus activity was confirmed in a previous study of the drug, and in the expanded-access study, treatment was associated with improved survival vs. historical data.

Up to 100 patients will be enrolled in the current pilot portion of the study, and the findings will be used to guide the second half of the phase III study, she said, noting that as of September, 48 subjects from 17 centers had been enrolled.

“Brincidofovir demonstrated potent virologic activity in patients with adenovirus disease. Subjects treated with brincidofovir appeared to have improved survival vs. historical controls, and there were no new safety signals identified. The data from the pilot portion of this study clearly support progression to the design of the next half of this phase III study for brincidofovir among adenovirus-infected patients,” she concluded.

Dr. Young reported being a clinical investigator and/or receiving research support from Chimerix, GlaxoSmithKline, Merck, and ViroPharma.

PHILADELPHIA – Brincidofovir, an orally available lipid conjugate of cidofovir, appears promising for the treatment of adenovirus infection in children and young adults, according to findings from the open-label pilot portion of a phase III study.

Of 26 patients from birth through age 29 years who were enrolled in the study as of July 15, 13 discontinued treatment prematurely, 4 completed treatment, and 9 continued with treatment. Plasma viral load decreased over time in most of the 13 patients who either completed or remained on treatment, Dr. Jo-Anne Young reported at an annual scientific meeting on infectious diseases.

After a median treatment duration of 54 days, clearance of adenovirus from respiratory secretions, urine, and stool among those patients in whom these values were measured at baseline was 42%, 33%, and 27%, respectively. Mortality was 46% among all 26 patients and was 38% among patients with disseminated disease. In a prior expanded-access trial of the drug, mortality was 51% in treated patients with disseminated disease, and in a historical cohort from a 2003 study of patients with disseminated disease, mortality at 1 year was 82%.

Of note, one patient in the current study experienced an increase in viral load; that patient had received prior treatment with brincidofovir, and was found to have a T87I mutation with known resistance to cidofovir and brincidofovir. Six other patients with prior cidofovir exposure reached undetectable levels of adenovirus, and one had a greater than 2-log decline, so the effect of prior exposure on treatment response remains uncertain, Dr. Young of the University of Minnesota Medical Center, Minneapolis, said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Another trend that was noted in the current study was a possible increase in viral load prior to a decline in viral load. In one case this occurred in association with treatment interruption due to moderate hyperbilirubinemia, but the viral load declined again once treatment was restarted, and was undetectable by the 8th week of treatment.

Most of the patients in the study to date (80%) were children, 65% were males, 65% were white, and 65% had disseminated infection with two or more body systems affected. Most of those were high-risk patients, who had received hematopoietic stem cell transplants from unrelated donors, Dr. Young noted.

Half of the patients had a high viral copy load in their blood, and many had multiple viruses detected. For example, 27% had BK virus in their urine, 19% had cytomegalovirus detected in their plasma, and 8% had Epstein-Barr virus detected in their plasma .

Treatment was given as a twice-weekly 100-mg dose in adults weighing at least 50 kg, and as a twice-weekly, 2-mg/kg dose in children under age 12 or weighing less than 50 kg. Treatment duration was 12 weeks, and patients were followed for an additional 24 weeks.

Of the 13 patients who discontinued treatment, 4 died, 3 discontinued because of an adverse event (including 2 cases of diarrhea considered treatment related and 1 case of liver function testing abnormalities deemed unrelated to treatment), 2 discontinued on physician advice, 2 started other therapy, 1 experienced progression of transplant qualifying disease, and 1 withdrew consent for study participation. Among those who continued, median treatment duration was 54 days at the time the data were presented.

“Adenovirus is an infection with a high unmet medical treatment need,” Dr. Young said, noting that it is associated with a wide spectrum of disease, ranging from asymptomatic viremia to disseminated disease, particularly among hematopoietic stem cell transplant recipients.

The reported incidence varies from 5% to 50%, and mortality ranges from 26% for untreated symptomatic infection to 80% for disseminated disease.

Risk factors include pediatric age, high-risk types of allogeneic transplants, and the presence of acute graft vs. host disease in any transplant recipient.

Current treatment strategies involve supportive care with a reduction in immune suppression and/or initiation of direct antiviral treatment – typically intravenous cidofovir, which is associated with a risk of significant renal injury, Dr. Young said.

Brincidofovir, however, allows for oral dosing and high intracellular uptake, delivering high intracellular levels of the active antiviral, she noted, adding that there is no evidence of nephrotoxicity or hematologic toxicity associated with brincidofovir.

Antiadenovirus activity was confirmed in a previous study of the drug, and in the expanded-access study, treatment was associated with improved survival vs. historical data.

Up to 100 patients will be enrolled in the current pilot portion of the study, and the findings will be used to guide the second half of the phase III study, she said, noting that as of September, 48 subjects from 17 centers had been enrolled.

“Brincidofovir demonstrated potent virologic activity in patients with adenovirus disease. Subjects treated with brincidofovir appeared to have improved survival vs. historical controls, and there were no new safety signals identified. The data from the pilot portion of this study clearly support progression to the design of the next half of this phase III study for brincidofovir among adenovirus-infected patients,” she concluded.

Dr. Young reported being a clinical investigator and/or receiving research support from Chimerix, GlaxoSmithKline, Merck, and ViroPharma.

PHILADELPHIA – Brincidofovir, an orally available lipid conjugate of cidofovir, appears promising for the treatment of adenovirus infection in children and young adults, according to findings from the open-label pilot portion of a phase III study.

Of 26 patients from birth through age 29 years who were enrolled in the study as of July 15, 13 discontinued treatment prematurely, 4 completed treatment, and 9 continued with treatment. Plasma viral load decreased over time in most of the 13 patients who either completed or remained on treatment, Dr. Jo-Anne Young reported at an annual scientific meeting on infectious diseases.

After a median treatment duration of 54 days, clearance of adenovirus from respiratory secretions, urine, and stool among those patients in whom these values were measured at baseline was 42%, 33%, and 27%, respectively. Mortality was 46% among all 26 patients and was 38% among patients with disseminated disease. In a prior expanded-access trial of the drug, mortality was 51% in treated patients with disseminated disease, and in a historical cohort from a 2003 study of patients with disseminated disease, mortality at 1 year was 82%.

Of note, one patient in the current study experienced an increase in viral load; that patient had received prior treatment with brincidofovir, and was found to have a T87I mutation with known resistance to cidofovir and brincidofovir. Six other patients with prior cidofovir exposure reached undetectable levels of adenovirus, and one had a greater than 2-log decline, so the effect of prior exposure on treatment response remains uncertain, Dr. Young of the University of Minnesota Medical Center, Minneapolis, said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Another trend that was noted in the current study was a possible increase in viral load prior to a decline in viral load. In one case this occurred in association with treatment interruption due to moderate hyperbilirubinemia, but the viral load declined again once treatment was restarted, and was undetectable by the 8th week of treatment.

Most of the patients in the study to date (80%) were children, 65% were males, 65% were white, and 65% had disseminated infection with two or more body systems affected. Most of those were high-risk patients, who had received hematopoietic stem cell transplants from unrelated donors, Dr. Young noted.

Half of the patients had a high viral copy load in their blood, and many had multiple viruses detected. For example, 27% had BK virus in their urine, 19% had cytomegalovirus detected in their plasma, and 8% had Epstein-Barr virus detected in their plasma .

Treatment was given as a twice-weekly 100-mg dose in adults weighing at least 50 kg, and as a twice-weekly, 2-mg/kg dose in children under age 12 or weighing less than 50 kg. Treatment duration was 12 weeks, and patients were followed for an additional 24 weeks.

Of the 13 patients who discontinued treatment, 4 died, 3 discontinued because of an adverse event (including 2 cases of diarrhea considered treatment related and 1 case of liver function testing abnormalities deemed unrelated to treatment), 2 discontinued on physician advice, 2 started other therapy, 1 experienced progression of transplant qualifying disease, and 1 withdrew consent for study participation. Among those who continued, median treatment duration was 54 days at the time the data were presented.

“Adenovirus is an infection with a high unmet medical treatment need,” Dr. Young said, noting that it is associated with a wide spectrum of disease, ranging from asymptomatic viremia to disseminated disease, particularly among hematopoietic stem cell transplant recipients.

The reported incidence varies from 5% to 50%, and mortality ranges from 26% for untreated symptomatic infection to 80% for disseminated disease.

Risk factors include pediatric age, high-risk types of allogeneic transplants, and the presence of acute graft vs. host disease in any transplant recipient.

Current treatment strategies involve supportive care with a reduction in immune suppression and/or initiation of direct antiviral treatment – typically intravenous cidofovir, which is associated with a risk of significant renal injury, Dr. Young said.

Brincidofovir, however, allows for oral dosing and high intracellular uptake, delivering high intracellular levels of the active antiviral, she noted, adding that there is no evidence of nephrotoxicity or hematologic toxicity associated with brincidofovir.

Antiadenovirus activity was confirmed in a previous study of the drug, and in the expanded-access study, treatment was associated with improved survival vs. historical data.

Up to 100 patients will be enrolled in the current pilot portion of the study, and the findings will be used to guide the second half of the phase III study, she said, noting that as of September, 48 subjects from 17 centers had been enrolled.

“Brincidofovir demonstrated potent virologic activity in patients with adenovirus disease. Subjects treated with brincidofovir appeared to have improved survival vs. historical controls, and there were no new safety signals identified. The data from the pilot portion of this study clearly support progression to the design of the next half of this phase III study for brincidofovir among adenovirus-infected patients,” she concluded.

Dr. Young reported being a clinical investigator and/or receiving research support from Chimerix, GlaxoSmithKline, Merck, and ViroPharma.

PHILADELPHIA – ALS-008176, an oral prodrug of the novel cytidine nucleoside analog, rapidly reduced respiratory syncitial virus load and clinical disease severity in healthy adult volunteers infected with a clinical strain of the virus as part of a double-blind, placebo-controlled phase IIa study.

Of 62 adults aged 18-45 years with preexisting RSV-A specific antibody titers who were inoculated with RSV-A Memphis 37b virus and randomized to receive placebo or one of three ALS-008176 dosing regimens, 35 met the criteria for infection. The viral load area under the curve (AUC) was significantly and rapidly reduced in all volunteers who received ALS-008176, compared with those who received placebo; the reduction in AUC, compared with placebo, ranged from 73% to 88% for the treatment groups at day 12 , Dr. John DeVincenzo of the University of Tennessee Health Science Center, Memphis, reported at an annual scientific meeting on infectious diseases.

Further, the AUC for symptom scores and mucous quantity as measured by weight were also reduced for all treatment groups, compared with placebo, and no subjects exhibited viral load rebound at days 16 or 28 after dosing, Dr. DeVincenzo said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

The study subjects, who had RSV-A specific antibody titers in the lowest 25th percentile of the population, were inoculated at baseline and monitored for RSV infection in nasal wash every 12 hours. At either 12 hours after infection was detected or 6 days following inoculation – whichever came first – they were randomized to receive either placebo or ALS-008176 given as a loading dose of 750 mg followed by 500-mg maintenance doses, a loading dose of 750 mg followed by 150-mg maintenance doses, or 375 mg every 12 hours for 5 days. The treatment and placebo groups were well balanced with respect to age, body mass index, sex, and viral load. Assessment of viral load, RSV symptom scores, and mucous weight were evaluated multiple times daily for 12 days, then again on days 16 and 28.

A decrease in viral load in the treatment groups occurred as early as day 0.5 after the initial dose, whereas the viral load in the placebo group increased to more than 4 logs, peaking at day 3.5 and then dropping. The most dramatic decrease in viral load was seen in the highest-dose group and was better in both groups that received a loading dose than in the treatment group that did not.

Viral load in the treatment groups became undetectable very quickly, Dr. DeVincenzo said, noting that levels remained undetectable at days 16 and 28, indicating there was no rebound after dosing was stopped.

No viral resistance mutations were noted.

Treatment with ALS-008176, which is a potent and selective inhibitor of RSV RNA-dependent RNA polymerase that is active against multiple A and B strains of RSV, was well tolerated; no clinically significant laboratory abnormalities occurred, and adverse events all were mild or moderate and were generally balanced between the placebo and treatment groups. None of the volunteers discontinued the study because of adverse events, Dr. DeVincenzo said.

The findings are encouraging given the lack of an effective treatment or vaccine for RSV, which is an important cause of morbidity and mortality worldwide – particularly in infants.

“Further studies of ALS-008176 in natural infections are warranted,” he said, noting that such studies are currently ongoing, including one in otherwise healthy infants hospitalized with RSV.

Dr. DeVincenzo is a consultant for, and/or has received research support from, Abbvie, Alios Biopharma, Alnylam, Ark Pharma, Astra Zeneca, Biota, Crucell, the Genomics Institute of the Novartis Research Foundation, Gilead Sciences, Janssen, MedImmune, Retroscreen Virology, Teva, and Novartis.

PHILADELPHIA – ALS-008176, an oral prodrug of the novel cytidine nucleoside analog, rapidly reduced respiratory syncitial virus load and clinical disease severity in healthy adult volunteers infected with a clinical strain of the virus as part of a double-blind, placebo-controlled phase IIa study.

Of 62 adults aged 18-45 years with preexisting RSV-A specific antibody titers who were inoculated with RSV-A Memphis 37b virus and randomized to receive placebo or one of three ALS-008176 dosing regimens, 35 met the criteria for infection. The viral load area under the curve (AUC) was significantly and rapidly reduced in all volunteers who received ALS-008176, compared with those who received placebo; the reduction in AUC, compared with placebo, ranged from 73% to 88% for the treatment groups at day 12 , Dr. John DeVincenzo of the University of Tennessee Health Science Center, Memphis, reported at an annual scientific meeting on infectious diseases.

Further, the AUC for symptom scores and mucous quantity as measured by weight were also reduced for all treatment groups, compared with placebo, and no subjects exhibited viral load rebound at days 16 or 28 after dosing, Dr. DeVincenzo said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

The study subjects, who had RSV-A specific antibody titers in the lowest 25th percentile of the population, were inoculated at baseline and monitored for RSV infection in nasal wash every 12 hours. At either 12 hours after infection was detected or 6 days following inoculation – whichever came first – they were randomized to receive either placebo or ALS-008176 given as a loading dose of 750 mg followed by 500-mg maintenance doses, a loading dose of 750 mg followed by 150-mg maintenance doses, or 375 mg every 12 hours for 5 days. The treatment and placebo groups were well balanced with respect to age, body mass index, sex, and viral load. Assessment of viral load, RSV symptom scores, and mucous weight were evaluated multiple times daily for 12 days, then again on days 16 and 28.

A decrease in viral load in the treatment groups occurred as early as day 0.5 after the initial dose, whereas the viral load in the placebo group increased to more than 4 logs, peaking at day 3.5 and then dropping. The most dramatic decrease in viral load was seen in the highest-dose group and was better in both groups that received a loading dose than in the treatment group that did not.

Viral load in the treatment groups became undetectable very quickly, Dr. DeVincenzo said, noting that levels remained undetectable at days 16 and 28, indicating there was no rebound after dosing was stopped.

No viral resistance mutations were noted.

Treatment with ALS-008176, which is a potent and selective inhibitor of RSV RNA-dependent RNA polymerase that is active against multiple A and B strains of RSV, was well tolerated; no clinically significant laboratory abnormalities occurred, and adverse events all were mild or moderate and were generally balanced between the placebo and treatment groups. None of the volunteers discontinued the study because of adverse events, Dr. DeVincenzo said.

The findings are encouraging given the lack of an effective treatment or vaccine for RSV, which is an important cause of morbidity and mortality worldwide – particularly in infants.

“Further studies of ALS-008176 in natural infections are warranted,” he said, noting that such studies are currently ongoing, including one in otherwise healthy infants hospitalized with RSV.

Dr. DeVincenzo is a consultant for, and/or has received research support from, Abbvie, Alios Biopharma, Alnylam, Ark Pharma, Astra Zeneca, Biota, Crucell, the Genomics Institute of the Novartis Research Foundation, Gilead Sciences, Janssen, MedImmune, Retroscreen Virology, Teva, and Novartis.

PHILADELPHIA – ALS-008176, an oral prodrug of the novel cytidine nucleoside analog, rapidly reduced respiratory syncitial virus load and clinical disease severity in healthy adult volunteers infected with a clinical strain of the virus as part of a double-blind, placebo-controlled phase IIa study.

Of 62 adults aged 18-45 years with preexisting RSV-A specific antibody titers who were inoculated with RSV-A Memphis 37b virus and randomized to receive placebo or one of three ALS-008176 dosing regimens, 35 met the criteria for infection. The viral load area under the curve (AUC) was significantly and rapidly reduced in all volunteers who received ALS-008176, compared with those who received placebo; the reduction in AUC, compared with placebo, ranged from 73% to 88% for the treatment groups at day 12 , Dr. John DeVincenzo of the University of Tennessee Health Science Center, Memphis, reported at an annual scientific meeting on infectious diseases.

Further, the AUC for symptom scores and mucous quantity as measured by weight were also reduced for all treatment groups, compared with placebo, and no subjects exhibited viral load rebound at days 16 or 28 after dosing, Dr. DeVincenzo said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

The study subjects, who had RSV-A specific antibody titers in the lowest 25th percentile of the population, were inoculated at baseline and monitored for RSV infection in nasal wash every 12 hours. At either 12 hours after infection was detected or 6 days following inoculation – whichever came first – they were randomized to receive either placebo or ALS-008176 given as a loading dose of 750 mg followed by 500-mg maintenance doses, a loading dose of 750 mg followed by 150-mg maintenance doses, or 375 mg every 12 hours for 5 days. The treatment and placebo groups were well balanced with respect to age, body mass index, sex, and viral load. Assessment of viral load, RSV symptom scores, and mucous weight were evaluated multiple times daily for 12 days, then again on days 16 and 28.

A decrease in viral load in the treatment groups occurred as early as day 0.5 after the initial dose, whereas the viral load in the placebo group increased to more than 4 logs, peaking at day 3.5 and then dropping. The most dramatic decrease in viral load was seen in the highest-dose group and was better in both groups that received a loading dose than in the treatment group that did not.

Viral load in the treatment groups became undetectable very quickly, Dr. DeVincenzo said, noting that levels remained undetectable at days 16 and 28, indicating there was no rebound after dosing was stopped.

No viral resistance mutations were noted.

Treatment with ALS-008176, which is a potent and selective inhibitor of RSV RNA-dependent RNA polymerase that is active against multiple A and B strains of RSV, was well tolerated; no clinically significant laboratory abnormalities occurred, and adverse events all were mild or moderate and were generally balanced between the placebo and treatment groups. None of the volunteers discontinued the study because of adverse events, Dr. DeVincenzo said.

The findings are encouraging given the lack of an effective treatment or vaccine for RSV, which is an important cause of morbidity and mortality worldwide – particularly in infants.

“Further studies of ALS-008176 in natural infections are warranted,” he said, noting that such studies are currently ongoing, including one in otherwise healthy infants hospitalized with RSV.

Dr. DeVincenzo is a consultant for, and/or has received research support from, Abbvie, Alios Biopharma, Alnylam, Ark Pharma, Astra Zeneca, Biota, Crucell, the Genomics Institute of the Novartis Research Foundation, Gilead Sciences, Janssen, MedImmune, Retroscreen Virology, Teva, and Novartis.