Photo by Bill Branson

Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to research published in Blood Advances.

Researchers found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain.

“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” said study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens in Greece.

For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis.

They were randomized (in a double-blinded fashion) to receive 60 mg of denosumab (n=32) or placebo (n=31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.

Baseline characteristics were largely similar between the treatment arms.

However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm—68.48 IU/L and 85.45 IU/L, respectively (P=0.013).

And the mean value of the tartrate-resistant acid phosphatase isoform-5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm—0.42 IU/L and 0.16 IU/L, respectively (P=0.026).

Results

The researchers measured bone mineral density in the L1-L4 lumbar spine, the wrist, and the femoral neck.

At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P=0.043).

The mean decrease in wrist bone mineral density was -0.26% and -3.92%, respectively (P=0.035).

And the mean increase in femoral neck bone mineral density was 4.08% and 1.96%, respectively (P=0.870).

Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and Huskisson’s visual analog scale (P<0.001 for both).

However, there was no significant change in pain for patients in the placebo arm (P=0.356 with Huskisson’s and P=0.768 with McGill-Melzack).

At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline (P<0.001 for all) in several markers of bone remodeling, including:

• Soluble receptor activator of nuclear factor kappa-B ligand (sRANKL)
• Osteoprotegerin (OPG)
• sRANKL/OPG ratio
• C-terminal crosslinking telopeptide of type I collagen (CTX)
• TRACP-5b
• bALP.

There were no significant changes in dickkopf-1 (Dkk-1), sclerostin, or osteocalcin (OC) in the denosumab arm.

In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, Dkk-1, sclerostin, CTX, TRACP-5b, and bALP (P<0.001 for all). There was no significant change from baseline in the sRANKL/OPG ratio or OC.

In all, there were 17 adverse events (AEs) in 14 patients.

There were three grade 1 AEs in the placebo arm and 11 in the denosumab arm. Most grade 1 AEs in the denosumab arm were test abnormalities, although three were not—headache, diarrhea, and fever.

There were three serious AEs in the denosumab arm as well—pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these AEs were considered unrelated to denosumab.

This study was funded by Amgen, which markets denosumab as Xgeva. The authors said they had no competing financial interests.

Photo by Bill Branson

Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to research published in Blood Advances.

Researchers found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain.

“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” said study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens in Greece.

For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis.

They were randomized (in a double-blinded fashion) to receive 60 mg of denosumab (n=32) or placebo (n=31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.

Baseline characteristics were largely similar between the treatment arms.

However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm—68.48 IU/L and 85.45 IU/L, respectively (P=0.013).

And the mean value of the tartrate-resistant acid phosphatase isoform-5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm—0.42 IU/L and 0.16 IU/L, respectively (P=0.026).

Results

The researchers measured bone mineral density in the L1-L4 lumbar spine, the wrist, and the femoral neck.

At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P=0.043).

The mean decrease in wrist bone mineral density was -0.26% and -3.92%, respectively (P=0.035).

And the mean increase in femoral neck bone mineral density was 4.08% and 1.96%, respectively (P=0.870).

Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and Huskisson’s visual analog scale (P<0.001 for both).

However, there was no significant change in pain for patients in the placebo arm (P=0.356 with Huskisson’s and P=0.768 with McGill-Melzack).

At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline (P<0.001 for all) in several markers of bone remodeling, including:

• Soluble receptor activator of nuclear factor kappa-B ligand (sRANKL)
• Osteoprotegerin (OPG)
• sRANKL/OPG ratio
• C-terminal crosslinking telopeptide of type I collagen (CTX)
• TRACP-5b
• bALP.

There were no significant changes in dickkopf-1 (Dkk-1), sclerostin, or osteocalcin (OC) in the denosumab arm.

In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, Dkk-1, sclerostin, CTX, TRACP-5b, and bALP (P<0.001 for all). There was no significant change from baseline in the sRANKL/OPG ratio or OC.

In all, there were 17 adverse events (AEs) in 14 patients.

There were three grade 1 AEs in the placebo arm and 11 in the denosumab arm. Most grade 1 AEs in the denosumab arm were test abnormalities, although three were not—headache, diarrhea, and fever.

There were three serious AEs in the denosumab arm as well—pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these AEs were considered unrelated to denosumab.

This study was funded by Amgen, which markets denosumab as Xgeva. The authors said they had no competing financial interests.

Photo by Bill Branson

Denosumab can be effective against osteoporosis caused by transfusion-dependent thalassemia (TDT), according to research published in Blood Advances.

Researchers found that patients who received twice-yearly injections of denosumab experienced a significant increase in bone density and reduction in bone pain.

“Not only is denosumab associated with improved bone health and reduced pain, but its ease of administration may very well make this drug superior to bisphosphonates for the treatment of osteoporosis in patients with TDT and osteoporosis,” said study author Evangelos Terpos, MD, of the National and Kapodistrian University of Athens in Greece.

For this phase 2b study, Dr. Terpos and his colleagues evaluated 63 patients with TDT and osteoporosis.

They were randomized (in a double-blinded fashion) to receive 60 mg of denosumab (n=32) or placebo (n=31) on days 0 and 180 of a 12-month period. Patients in both arms also received daily supplements of calcium and vitamin D.

Baseline characteristics were largely similar between the treatment arms.

However, the mean value of bone-specific alkaline phosphatase (bALP) was significantly lower in the placebo arm than the denosumab arm—68.48 IU/L and 85.45 IU/L, respectively (P=0.013).

And the mean value of the tartrate-resistant acid phosphatase isoform-5b (TRACP-5b) marker was significantly higher in the denosumab arm than in the placebo arm—0.42 IU/L and 0.16 IU/L, respectively (P=0.026).

Results

The researchers measured bone mineral density in the L1-L4 lumbar spine, the wrist, and the femoral neck.

At 12 months, the mean increase in L1-L4 bone mineral density was 5.92% in the denosumab arm and 2.92% in the placebo arm (P=0.043).

The mean decrease in wrist bone mineral density was -0.26% and -3.92%, respectively (P=0.035).

And the mean increase in femoral neck bone mineral density was 4.08% and 1.96%, respectively (P=0.870).

Patients in the denosumab arm had a significant reduction in bone pain at 12 months, according to the McGill-Melzack scoring system and Huskisson’s visual analog scale (P<0.001 for both).

However, there was no significant change in pain for patients in the placebo arm (P=0.356 with Huskisson’s and P=0.768 with McGill-Melzack).

At 12 months, patients in the denosumab arm had experienced a significant reduction from baseline (P<0.001 for all) in several markers of bone remodeling, including:

• Soluble receptor activator of nuclear factor kappa-B ligand (sRANKL)
• Osteoprotegerin (OPG)
• sRANKL/OPG ratio
• C-terminal crosslinking telopeptide of type I collagen (CTX)
• TRACP-5b
• bALP.

There were no significant changes in dickkopf-1 (Dkk-1), sclerostin, or osteocalcin (OC) in the denosumab arm.

In the placebo arm, patients had a significant increase from baseline in several markers of bone remodeling, including sRANKL, OPG, Dkk-1, sclerostin, CTX, TRACP-5b, and bALP (P<0.001 for all). There was no significant change from baseline in the sRANKL/OPG ratio or OC.

In all, there were 17 adverse events (AEs) in 14 patients.

There were three grade 1 AEs in the placebo arm and 11 in the denosumab arm. Most grade 1 AEs in the denosumab arm were test abnormalities, although three were not—headache, diarrhea, and fever.

There were three serious AEs in the denosumab arm as well—pleural effusion (grade 3), atrial fibrillation (grade 3), and supraventricular tachycardia (grade 4). All three of these AEs were considered unrelated to denosumab.

This study was funded by Amgen, which markets denosumab as Xgeva. The authors said they had no competing financial interests.

Photo by Rhoda Baer

The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).

Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.

Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”

The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”

The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.

The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).

Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.

“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.

“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”

Photo by Rhoda Baer

The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).

Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.

Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”

The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”

The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.

The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).

Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.

“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.

“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”

Photo by Rhoda Baer

The U.S. Food and Drug Administration (FDA) and European Commission (EC) have approved Coherus BioSciences, Inc.’s pegfilgrastim-cbqv (Udenyca™), a biosimilar of Amgen’s pegfilgrastim product (Neulasta).

Both agencies approved pegfilgrastim-cbqv (formerly CHS-1701) for cancer patients receiving myelosuppressive chemotherapy.

Pegfilgrastim-cbqv is FDA-approved “to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia.”

The product is EC-approved to reduce “the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukemia and myelodysplastic syndromes).”

The U.S. prescribing information for pegfilgrastim-cbqv is available at www.UDENYCA.com, and the European summary of product characteristics is available on the European Medicines Agency’s website.

The FDA and EC approvals of pegfilgrastim-cbqv were supported by analyses establishing biosimilarity as well as pharmacokinetic, pharmacodynamic, and immunogenicity studies of healthy subjects (NCT02650973, NCT02385851, and NCT02418104).

Results from one of these studies (NCT02650973) were presented at the 2017 ASCO Annual Meeting.

“Udenyca’s robust clinical package includes a dedicated immunogenicity similarity study in over 300 healthy subjects,” said Barbara Finck, MD, chief medical officer of Coherus BioSciences.

“In support of that study, and as part of our commitment to ensuring patient safety, we deployed a battery of sensitive immunogenicity assays. This effort not only supported the biosimilarity of Udenyca but also advanced the understanding of the immunogenic response of pegfilgrastim products.”

MUNICH – Getting less than 6 hours of sleep nightly on a regular basis or waking up multiple times was independently associated with increased risk of subclinical atherosclerosis in the Spanish PESA study, Fernando Dominguez, MD, reported at the annual congress of the European Society of Cardiology.

Moreover, a graded response was evident in PESA (Progression of Early Subclinical Atherosclerosis): The more times an individual typically awoke per night, the greater the number of atherosclerotic carotid or femoral artery territories documented on three-dimensional vascular ultrasound, added Dr. Dominguez of the Spanish National Center for Cardiovascular Research in Madrid.

“These findings show that sleep is associated with cardiovascular health and suggest that the modification of abnormal sleep patterns may contribute to the reduction of burden of cardiovascular diseases,” the cardiologist said.

The cross-sectional PESA study, whose principal investigator was Valentin Fuster, MD, PhD, included 3,974 middle-aged Madrid bank employees free of known heart disease or history of stroke who wore a waistband activity monitor for a week to record sleep quantity and quality. They also underwent three-dimensional vascular ultrasound and measurement of coronary artery calcium.

PESA was one of several large studies presented at the meeting that focused on deviations from normal sleep as a marker for increased risk of cardiovascular disease and/or mortality. Of note, however, PESA was the only one to use activity monitoring technology to track sleep.

“It was essential to use objectively measured sleep variables, because they showed huge disparity with patients’ self-reports on sleep questionnaires,” Dr. Dominguez explained.

Indeed, while 10.7% of PESA participants self-reported sleeping less than 6 hours per night on the Sleep Habits Questionnaire, actigraphy showed the true rate was 27.1%.

Based on actigraphic findings, subjects were divided into tertiles based upon average hours of sleep per night, ranging from less than 6 to more than 8. They were also grouped in quintiles based upon their extent of fragmented sleep.

Subjects with short sleep were significantly older and more likely to have high blood pressure, a higher body mass index, and metabolic syndrome than those who averaged 7-8 hours of sleep. Individuals in the top quintile for sleep awakening were older and had higher prevalences of smoking and hypertension than those in the lowest quintile.

In multivariate analyses adjusted for these differences as well as for physical activity, depression, obstructive sleep apnea, daily calorie consumption, alcohol intake, and other potential confounders, subjects who slept less than 6 hours per night had a 27% greater volume of noncoronary plaque than those who slept 7-8 hours. They also had 21% more vascular territories laden with subclinical atherosclerosis. The risk of subclinical noncoronary atherosclerosis was greater among women who averaged less than 6 hours of sleep per night, representing a 48% relative risk increase in plaque volume, versus 21% in men.

At the other extreme, women who slept more than 8 hours per night had an 83% increased plaque volume, while men who slept that much had no increase in risk, compared with men who slept for 7-8 hours.

Subjects in the top quintile for sleep fragmentation had 34% more vascular territories affected by atherosclerosis than those in the lowest quintile. Their noncoronary plaque burden was 23% greater as well.
 

An 11-study meta-analysis

Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Center in Athens, presented a meta-analysis of 11 prospective studies of the relationship between daily sleep duration and cardiovascular disease morbidity and mortality published within the past 5 years, reflecting burgeoning interest in this hot-button topic. Collectively, the meta-analysis totaled 1,000,541 adults without baseline cardiovascular disease who were followed for an average of 9.3 years.

Swedes weigh in

Moa Bengtsson, a combined medical/PhD student at the University of Gothenburg (Sweden), presented a prospective study of 798 men who were 50 years old in 1993, when they underwent a physical examination and completed extensive lifestyle questionnaires that included average self-reported sleep duration. Among the 759 men still available for evaluation after 21 years, or nearly 15,000 person-years of followup, those who reported sleeping an average of 5 hours or less per night back at age 50 were 93% more likely to have experienced a major cardiovascular event by age 71 -- acute MI, stroke, coronary revascularization, heart failure hospitalization, or cardiovascular death -- compared with those who averaged 7-8 hours of shut eye.

[email protected]

MUNICH – Getting less than 6 hours of sleep nightly on a regular basis or waking up multiple times was independently associated with increased risk of subclinical atherosclerosis in the Spanish PESA study, Fernando Dominguez, MD, reported at the annual congress of the European Society of Cardiology.

Moreover, a graded response was evident in PESA (Progression of Early Subclinical Atherosclerosis): The more times an individual typically awoke per night, the greater the number of atherosclerotic carotid or femoral artery territories documented on three-dimensional vascular ultrasound, added Dr. Dominguez of the Spanish National Center for Cardiovascular Research in Madrid.

“These findings show that sleep is associated with cardiovascular health and suggest that the modification of abnormal sleep patterns may contribute to the reduction of burden of cardiovascular diseases,” the cardiologist said.

The cross-sectional PESA study, whose principal investigator was Valentin Fuster, MD, PhD, included 3,974 middle-aged Madrid bank employees free of known heart disease or history of stroke who wore a waistband activity monitor for a week to record sleep quantity and quality. They also underwent three-dimensional vascular ultrasound and measurement of coronary artery calcium.

PESA was one of several large studies presented at the meeting that focused on deviations from normal sleep as a marker for increased risk of cardiovascular disease and/or mortality. Of note, however, PESA was the only one to use activity monitoring technology to track sleep.

“It was essential to use objectively measured sleep variables, because they showed huge disparity with patients’ self-reports on sleep questionnaires,” Dr. Dominguez explained.

Indeed, while 10.7% of PESA participants self-reported sleeping less than 6 hours per night on the Sleep Habits Questionnaire, actigraphy showed the true rate was 27.1%.

Based on actigraphic findings, subjects were divided into tertiles based upon average hours of sleep per night, ranging from less than 6 to more than 8. They were also grouped in quintiles based upon their extent of fragmented sleep.

Subjects with short sleep were significantly older and more likely to have high blood pressure, a higher body mass index, and metabolic syndrome than those who averaged 7-8 hours of sleep. Individuals in the top quintile for sleep awakening were older and had higher prevalences of smoking and hypertension than those in the lowest quintile.

In multivariate analyses adjusted for these differences as well as for physical activity, depression, obstructive sleep apnea, daily calorie consumption, alcohol intake, and other potential confounders, subjects who slept less than 6 hours per night had a 27% greater volume of noncoronary plaque than those who slept 7-8 hours. They also had 21% more vascular territories laden with subclinical atherosclerosis. The risk of subclinical noncoronary atherosclerosis was greater among women who averaged less than 6 hours of sleep per night, representing a 48% relative risk increase in plaque volume, versus 21% in men.

At the other extreme, women who slept more than 8 hours per night had an 83% increased plaque volume, while men who slept that much had no increase in risk, compared with men who slept for 7-8 hours.

Subjects in the top quintile for sleep fragmentation had 34% more vascular territories affected by atherosclerosis than those in the lowest quintile. Their noncoronary plaque burden was 23% greater as well.
 

An 11-study meta-analysis

Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Center in Athens, presented a meta-analysis of 11 prospective studies of the relationship between daily sleep duration and cardiovascular disease morbidity and mortality published within the past 5 years, reflecting burgeoning interest in this hot-button topic. Collectively, the meta-analysis totaled 1,000,541 adults without baseline cardiovascular disease who were followed for an average of 9.3 years.

Swedes weigh in

Moa Bengtsson, a combined medical/PhD student at the University of Gothenburg (Sweden), presented a prospective study of 798 men who were 50 years old in 1993, when they underwent a physical examination and completed extensive lifestyle questionnaires that included average self-reported sleep duration. Among the 759 men still available for evaluation after 21 years, or nearly 15,000 person-years of followup, those who reported sleeping an average of 5 hours or less per night back at age 50 were 93% more likely to have experienced a major cardiovascular event by age 71 -- acute MI, stroke, coronary revascularization, heart failure hospitalization, or cardiovascular death -- compared with those who averaged 7-8 hours of shut eye.

[email protected]

MUNICH – Getting less than 6 hours of sleep nightly on a regular basis or waking up multiple times was independently associated with increased risk of subclinical atherosclerosis in the Spanish PESA study, Fernando Dominguez, MD, reported at the annual congress of the European Society of Cardiology.

Moreover, a graded response was evident in PESA (Progression of Early Subclinical Atherosclerosis): The more times an individual typically awoke per night, the greater the number of atherosclerotic carotid or femoral artery territories documented on three-dimensional vascular ultrasound, added Dr. Dominguez of the Spanish National Center for Cardiovascular Research in Madrid.

“These findings show that sleep is associated with cardiovascular health and suggest that the modification of abnormal sleep patterns may contribute to the reduction of burden of cardiovascular diseases,” the cardiologist said.

The cross-sectional PESA study, whose principal investigator was Valentin Fuster, MD, PhD, included 3,974 middle-aged Madrid bank employees free of known heart disease or history of stroke who wore a waistband activity monitor for a week to record sleep quantity and quality. They also underwent three-dimensional vascular ultrasound and measurement of coronary artery calcium.

PESA was one of several large studies presented at the meeting that focused on deviations from normal sleep as a marker for increased risk of cardiovascular disease and/or mortality. Of note, however, PESA was the only one to use activity monitoring technology to track sleep.

“It was essential to use objectively measured sleep variables, because they showed huge disparity with patients’ self-reports on sleep questionnaires,” Dr. Dominguez explained.

Indeed, while 10.7% of PESA participants self-reported sleeping less than 6 hours per night on the Sleep Habits Questionnaire, actigraphy showed the true rate was 27.1%.

Based on actigraphic findings, subjects were divided into tertiles based upon average hours of sleep per night, ranging from less than 6 to more than 8. They were also grouped in quintiles based upon their extent of fragmented sleep.

Subjects with short sleep were significantly older and more likely to have high blood pressure, a higher body mass index, and metabolic syndrome than those who averaged 7-8 hours of sleep. Individuals in the top quintile for sleep awakening were older and had higher prevalences of smoking and hypertension than those in the lowest quintile.

In multivariate analyses adjusted for these differences as well as for physical activity, depression, obstructive sleep apnea, daily calorie consumption, alcohol intake, and other potential confounders, subjects who slept less than 6 hours per night had a 27% greater volume of noncoronary plaque than those who slept 7-8 hours. They also had 21% more vascular territories laden with subclinical atherosclerosis. The risk of subclinical noncoronary atherosclerosis was greater among women who averaged less than 6 hours of sleep per night, representing a 48% relative risk increase in plaque volume, versus 21% in men.

At the other extreme, women who slept more than 8 hours per night had an 83% increased plaque volume, while men who slept that much had no increase in risk, compared with men who slept for 7-8 hours.

Subjects in the top quintile for sleep fragmentation had 34% more vascular territories affected by atherosclerosis than those in the lowest quintile. Their noncoronary plaque burden was 23% greater as well.
 

An 11-study meta-analysis

Epameinondas Fountas, MD, of the Onassis Cardiac Surgery Center in Athens, presented a meta-analysis of 11 prospective studies of the relationship between daily sleep duration and cardiovascular disease morbidity and mortality published within the past 5 years, reflecting burgeoning interest in this hot-button topic. Collectively, the meta-analysis totaled 1,000,541 adults without baseline cardiovascular disease who were followed for an average of 9.3 years.

Swedes weigh in

Moa Bengtsson, a combined medical/PhD student at the University of Gothenburg (Sweden), presented a prospective study of 798 men who were 50 years old in 1993, when they underwent a physical examination and completed extensive lifestyle questionnaires that included average self-reported sleep duration. Among the 759 men still available for evaluation after 21 years, or nearly 15,000 person-years of followup, those who reported sleeping an average of 5 hours or less per night back at age 50 were 93% more likely to have experienced a major cardiovascular event by age 71 -- acute MI, stroke, coronary revascularization, heart failure hospitalization, or cardiovascular death -- compared with those who averaged 7-8 hours of shut eye.

[email protected]

SAN ANTONIO – Opioids do not mix well with sleep, interfering with breathing and increasing the risk of central sleep apnea, explained Anita Rajagopal, MD, a pulmonologist in private practice in Indianapolis.

“The chronic respiratory suppressant effects of opioids are well described,” Dr. Rajagopal told attendees at the annual meeting of the American College of Chest Physicians. “The most characteristic signs of chronic opioid effects are irregular central apneas, ataxic breathing, Biot’s respiration and hypoxemia, mainly during NREM sleep.”

Dr. Rajagopal reviewed the research on the effects of opioid use, primarily for therapeutic use, during sleep, especially highlighting the adverse respiratory effects.

In one small study of 24 patients, ages 18-75, who were taking long-term opioids for chronic pain, 46% had severe sleep-disordered breathing, defined as an apnea-hypopnea index greater than 30/hour (J Clin Sleep Med. 2014 Aug 15;10[8]:847-52).

When compared to sleep clinic patients referred for sleep disordered breathing, the participants taking opioids had a higher frequency of central apneas and a lower arousal index. Further, the researchers found that “morphine equivalent doses correlated with the severity of sleep-disordered breathing.”

In another study, a systematic review from 2015, researchers sought to characterize the clinical features of sleep-disordered breathing associated with chronic opioid therapy (Anesth Analg. 2015 Jun;120[6]:1273-85). They identified eight studies with 560 patients, about a quarter of whom (24%) had central sleep apnea.

Once again, “The morphine equivalent daily dose was strongly associated with the severity of the sleep disordered breathing, predominantly central sleep apnea, with a morphine equivalent daily dose of more than 200 mg being a threshold of particular concern,” the researchers reported.

Patients receiving methadone therapy for heroin addiction are not spared the respiratory risks of opioids during sleep. Dr. Rajagopal shared research revealing that patients receiving methadone treatment for at least two months had a blunted hypercapnic respiratory response and increased hypoxemic ventilatory response, changes related to respiratory rate but not tidal volume.

“All mu-opioid receptor agonists can cause complex and potentially lethal effects on respiration during sleep,” Dr. Rajagopal said as she shared evidence from a 2007 study that compared breathing patterns during sleep between 60 patients taking chronic opioids and 60 matched patients not taking opioids (J Clin Sleep Med. 2007 Aug 15;3[5]:455-61).

That study found chronic opioid use to be associated with increased central apneas and reduced arterial oxygen saturation during wakefulness and NREM sleep. Again, a dose-response relationship emerged between morphine dose equivalent and the apnea-hypopnea, obstructive apnea, hypopnea and central apnea indices (P less than .001).

Patients who took opioids long-term were also more likely to have ataxic or irregular breathing during NREM sleep, compared with patients not taking opioids.

In yet another meta-analysis and systematic review she related, researchers found across 803 patients in seven studies that long-term opioids users had a modestly increased risk for central sleep apnea but no similar increased risk for obstructive sleep apnea (J Clin Sleep Med. 2016 Apr 15;12[4]:617-25).

“REM and slow-wave sleep are decreased across all categories of opioid use — intravenous morphine, oral morphine, or methadone and heroin,” she said.

Since some patients are still going to need opioids, such as methadone therapy for those recovering from opioid use disorder, it’s important to understand appropriate effective treatments for central sleep apnea.

“CPAP [continuous positive airway pressure] is generally ineffective for opioid-induced sleep apnea and may augment central events,” Dr. Rajagopal explained, but adaptive servo ventilation (ASV) is effective for opioid-induced central apneas.

In one study of 20 patients receiving opioid therapy and referred for obstructive apnea, for example, the participants were diagnosed instead with central sleep apnea (J Clin Sleep Med. 2014 Jun 15;10[6]:637-43). The 16 patients who received CPAP continued to show central sleep apnea, with an AHI of 34 events/hour and central-apnea index (CAI) of 20 events/hour. Even after a four-week break before restarting CPAP, patients’ apnea did not resolve.

After receiving ASV, however, the average AHI dropped to 11 events/hour and CAI dropped to 0 events/hour. Those changes were accompanied by improvements in oxygen saturation, with the oxyhemoglobin saturation nadir increasing from 83% to 90%.

Similarly, a prospective multi-center observational trial assessed 27 patients with central apnea after they used ASV at home for three months (Chest. 2015 Dec;148[6]:1454-1461). The participants began with an average AHI of 55 and CAI of 23 at baseline. CPAP dropped these values only to an AHI of 33 and CAI of 10, but treatment with ASV dropped them to an AHI of 4 and CAI of 0 (P less than .001).

SAN ANTONIO – Opioids do not mix well with sleep, interfering with breathing and increasing the risk of central sleep apnea, explained Anita Rajagopal, MD, a pulmonologist in private practice in Indianapolis.

“The chronic respiratory suppressant effects of opioids are well described,” Dr. Rajagopal told attendees at the annual meeting of the American College of Chest Physicians. “The most characteristic signs of chronic opioid effects are irregular central apneas, ataxic breathing, Biot’s respiration and hypoxemia, mainly during NREM sleep.”

Dr. Rajagopal reviewed the research on the effects of opioid use, primarily for therapeutic use, during sleep, especially highlighting the adverse respiratory effects.

In one small study of 24 patients, ages 18-75, who were taking long-term opioids for chronic pain, 46% had severe sleep-disordered breathing, defined as an apnea-hypopnea index greater than 30/hour (J Clin Sleep Med. 2014 Aug 15;10[8]:847-52).

When compared to sleep clinic patients referred for sleep disordered breathing, the participants taking opioids had a higher frequency of central apneas and a lower arousal index. Further, the researchers found that “morphine equivalent doses correlated with the severity of sleep-disordered breathing.”

In another study, a systematic review from 2015, researchers sought to characterize the clinical features of sleep-disordered breathing associated with chronic opioid therapy (Anesth Analg. 2015 Jun;120[6]:1273-85). They identified eight studies with 560 patients, about a quarter of whom (24%) had central sleep apnea.

Once again, “The morphine equivalent daily dose was strongly associated with the severity of the sleep disordered breathing, predominantly central sleep apnea, with a morphine equivalent daily dose of more than 200 mg being a threshold of particular concern,” the researchers reported.

Patients receiving methadone therapy for heroin addiction are not spared the respiratory risks of opioids during sleep. Dr. Rajagopal shared research revealing that patients receiving methadone treatment for at least two months had a blunted hypercapnic respiratory response and increased hypoxemic ventilatory response, changes related to respiratory rate but not tidal volume.

“All mu-opioid receptor agonists can cause complex and potentially lethal effects on respiration during sleep,” Dr. Rajagopal said as she shared evidence from a 2007 study that compared breathing patterns during sleep between 60 patients taking chronic opioids and 60 matched patients not taking opioids (J Clin Sleep Med. 2007 Aug 15;3[5]:455-61).

That study found chronic opioid use to be associated with increased central apneas and reduced arterial oxygen saturation during wakefulness and NREM sleep. Again, a dose-response relationship emerged between morphine dose equivalent and the apnea-hypopnea, obstructive apnea, hypopnea and central apnea indices (P less than .001).

Patients who took opioids long-term were also more likely to have ataxic or irregular breathing during NREM sleep, compared with patients not taking opioids.

In yet another meta-analysis and systematic review she related, researchers found across 803 patients in seven studies that long-term opioids users had a modestly increased risk for central sleep apnea but no similar increased risk for obstructive sleep apnea (J Clin Sleep Med. 2016 Apr 15;12[4]:617-25).

“REM and slow-wave sleep are decreased across all categories of opioid use — intravenous morphine, oral morphine, or methadone and heroin,” she said.

Since some patients are still going to need opioids, such as methadone therapy for those recovering from opioid use disorder, it’s important to understand appropriate effective treatments for central sleep apnea.

“CPAP [continuous positive airway pressure] is generally ineffective for opioid-induced sleep apnea and may augment central events,” Dr. Rajagopal explained, but adaptive servo ventilation (ASV) is effective for opioid-induced central apneas.

In one study of 20 patients receiving opioid therapy and referred for obstructive apnea, for example, the participants were diagnosed instead with central sleep apnea (J Clin Sleep Med. 2014 Jun 15;10[6]:637-43). The 16 patients who received CPAP continued to show central sleep apnea, with an AHI of 34 events/hour and central-apnea index (CAI) of 20 events/hour. Even after a four-week break before restarting CPAP, patients’ apnea did not resolve.

After receiving ASV, however, the average AHI dropped to 11 events/hour and CAI dropped to 0 events/hour. Those changes were accompanied by improvements in oxygen saturation, with the oxyhemoglobin saturation nadir increasing from 83% to 90%.

Similarly, a prospective multi-center observational trial assessed 27 patients with central apnea after they used ASV at home for three months (Chest. 2015 Dec;148[6]:1454-1461). The participants began with an average AHI of 55 and CAI of 23 at baseline. CPAP dropped these values only to an AHI of 33 and CAI of 10, but treatment with ASV dropped them to an AHI of 4 and CAI of 0 (P less than .001).

SAN ANTONIO – Opioids do not mix well with sleep, interfering with breathing and increasing the risk of central sleep apnea, explained Anita Rajagopal, MD, a pulmonologist in private practice in Indianapolis.

“The chronic respiratory suppressant effects of opioids are well described,” Dr. Rajagopal told attendees at the annual meeting of the American College of Chest Physicians. “The most characteristic signs of chronic opioid effects are irregular central apneas, ataxic breathing, Biot’s respiration and hypoxemia, mainly during NREM sleep.”

Dr. Rajagopal reviewed the research on the effects of opioid use, primarily for therapeutic use, during sleep, especially highlighting the adverse respiratory effects.

In one small study of 24 patients, ages 18-75, who were taking long-term opioids for chronic pain, 46% had severe sleep-disordered breathing, defined as an apnea-hypopnea index greater than 30/hour (J Clin Sleep Med. 2014 Aug 15;10[8]:847-52).

When compared to sleep clinic patients referred for sleep disordered breathing, the participants taking opioids had a higher frequency of central apneas and a lower arousal index. Further, the researchers found that “morphine equivalent doses correlated with the severity of sleep-disordered breathing.”

In another study, a systematic review from 2015, researchers sought to characterize the clinical features of sleep-disordered breathing associated with chronic opioid therapy (Anesth Analg. 2015 Jun;120[6]:1273-85). They identified eight studies with 560 patients, about a quarter of whom (24%) had central sleep apnea.

Once again, “The morphine equivalent daily dose was strongly associated with the severity of the sleep disordered breathing, predominantly central sleep apnea, with a morphine equivalent daily dose of more than 200 mg being a threshold of particular concern,” the researchers reported.

Patients receiving methadone therapy for heroin addiction are not spared the respiratory risks of opioids during sleep. Dr. Rajagopal shared research revealing that patients receiving methadone treatment for at least two months had a blunted hypercapnic respiratory response and increased hypoxemic ventilatory response, changes related to respiratory rate but not tidal volume.

“All mu-opioid receptor agonists can cause complex and potentially lethal effects on respiration during sleep,” Dr. Rajagopal said as she shared evidence from a 2007 study that compared breathing patterns during sleep between 60 patients taking chronic opioids and 60 matched patients not taking opioids (J Clin Sleep Med. 2007 Aug 15;3[5]:455-61).

That study found chronic opioid use to be associated with increased central apneas and reduced arterial oxygen saturation during wakefulness and NREM sleep. Again, a dose-response relationship emerged between morphine dose equivalent and the apnea-hypopnea, obstructive apnea, hypopnea and central apnea indices (P less than .001).

Patients who took opioids long-term were also more likely to have ataxic or irregular breathing during NREM sleep, compared with patients not taking opioids.

In yet another meta-analysis and systematic review she related, researchers found across 803 patients in seven studies that long-term opioids users had a modestly increased risk for central sleep apnea but no similar increased risk for obstructive sleep apnea (J Clin Sleep Med. 2016 Apr 15;12[4]:617-25).

“REM and slow-wave sleep are decreased across all categories of opioid use — intravenous morphine, oral morphine, or methadone and heroin,” she said.

Since some patients are still going to need opioids, such as methadone therapy for those recovering from opioid use disorder, it’s important to understand appropriate effective treatments for central sleep apnea.

“CPAP [continuous positive airway pressure] is generally ineffective for opioid-induced sleep apnea and may augment central events,” Dr. Rajagopal explained, but adaptive servo ventilation (ASV) is effective for opioid-induced central apneas.

In one study of 20 patients receiving opioid therapy and referred for obstructive apnea, for example, the participants were diagnosed instead with central sleep apnea (J Clin Sleep Med. 2014 Jun 15;10[6]:637-43). The 16 patients who received CPAP continued to show central sleep apnea, with an AHI of 34 events/hour and central-apnea index (CAI) of 20 events/hour. Even after a four-week break before restarting CPAP, patients’ apnea did not resolve.

After receiving ASV, however, the average AHI dropped to 11 events/hour and CAI dropped to 0 events/hour. Those changes were accompanied by improvements in oxygen saturation, with the oxyhemoglobin saturation nadir increasing from 83% to 90%.

Similarly, a prospective multi-center observational trial assessed 27 patients with central apnea after they used ASV at home for three months (Chest. 2015 Dec;148[6]:1454-1461). The participants began with an average AHI of 55 and CAI of 23 at baseline. CPAP dropped these values only to an AHI of 33 and CAI of 10, but treatment with ASV dropped them to an AHI of 4 and CAI of 0 (P less than .001).

Exercise may be as effective as CPAP in improving obstructive sleep apnea and quality of life in patients with heart failure, according to a study published in the October issue of Chest [https://journal.chestnet.org/article/S0012-3692(18)30790-6/fulltext].

Researchers undertook a randomized, four-arm trial in 65 patients with heart failure and obstructive sleep apnea, which compared the effects of CPAP alone, exercise alone – consisting of three supervised sessions per week for three months, or CPAP plus exercise. A control group received education sessions on the importance of exercise.

The greatest reduction in mean apnea-hypopnea index was seen in the CPAP group, who experienced a mean decrease of 24 events per hour. The exercise plus CPAP group and the exercise only groups showed a mean decrease of 10 events per hour. In contrast, the control group showed no significant decrease in the number of events per hour of sleep.

The authors commented that the change in apnea-hypopnea index was due to reduction in obstructive apneas and hypopneas, and noted the “difficulty of accurately distinguishing obstructive from central hypopneas”.

All the active interventions were associated with significant decreases in arousal index and improvements in sleep-related saturation compared to the control intervention.

Exercise – both alone and with CPAP – was associated with an increase in maximum heart rate and peak VO2, and decrease in VE/VCO2 slope compared to the CPAP-alone and control groups.

“We found that peak oxygen consumption and muscle performance improved significantly only in the exercise groups, but not with CPAP alone, even though CPAP was most effective in attenuating OSA severity,” wrote Dr. Denise M. Servantes, from the Departamento de Psicobiologia at the Universidade Federal de São Paul in Brazil, and co-authors. “Because peak VO2 is an independent predictor of survival and crucial to the optimal timing of cardiac transplantation, these findings have important clinical implications, even in patients who are adherent to CPAP.”

A significant number of participants in the active intervention groups changed New York Heart Association functional class; the number of patients in the exercise group in class I went from 0%-88% by three months, in the CPAP group it increased from 0% to 47%, and in the CPAP plus exercise group, it increased from 0% to 73%.

The study also found evidence of a trend towards improved sexual function in the participants who undertook both exercise plus CPAP.

All patients in the intervention groups showed improvements in subjective daytime sleepiness and quality of life, although improvements in the Minnesota Living with Heart Failure Questionnaire and Short Form Health Survey (SF-36) were significant only in the two groups that did exercise.

“The data suggest that exercise could be a therapeutic option for patients with HF and OSA who refuse CPAP or are intolerant to it,” the authors wrote. “In this regard, a considerable number of patients with HF and OSA do not experience subjective excessive daytime sleepiness and consequently observe no immediate benefit from using CPAP, which could contribute to poor long-term adherence.”

Individuals in the exercise group showed a slight but significant weight reduction, and those who undertook the exercise program also showed significant improvements in muscle strength and endurance compared to the control group.

The authors commented that another study examining the impact of weight loss program in people with moderate to severe obstructive sleep apnea found weight loss only or combined interventions achieved benefits for C-reactive protein levels, insulin resistance, and serum triglyceride levels. But these benefits weren’t seen with CPAP alone.

“The results of that study, and the present one emphasize the importance of adjunctive therapy of OSA with weight loss and exercise when applicable.”

However they acknowledged that the short duration of the study, and small sample size were limitations, and that this was only a preliminary investigation.

No conflicts of interest were declared.

SOURCE: Servantes D et al. Chest, 2018; 154:808-817. https://doi.org/10.1016/j.chest.2018.05.011. https://journal.chestnet.org/article/S0012-3692(18)30790-6/fulltext

Exercise may be as effective as CPAP in improving obstructive sleep apnea and quality of life in patients with heart failure, according to a study published in the October issue of Chest [https://journal.chestnet.org/article/S0012-3692(18)30790-6/fulltext].

Researchers undertook a randomized, four-arm trial in 65 patients with heart failure and obstructive sleep apnea, which compared the effects of CPAP alone, exercise alone – consisting of three supervised sessions per week for three months, or CPAP plus exercise. A control group received education sessions on the importance of exercise.

The greatest reduction in mean apnea-hypopnea index was seen in the CPAP group, who experienced a mean decrease of 24 events per hour. The exercise plus CPAP group and the exercise only groups showed a mean decrease of 10 events per hour. In contrast, the control group showed no significant decrease in the number of events per hour of sleep.

The authors commented that the change in apnea-hypopnea index was due to reduction in obstructive apneas and hypopneas, and noted the “difficulty of accurately distinguishing obstructive from central hypopneas”.

All the active interventions were associated with significant decreases in arousal index and improvements in sleep-related saturation compared to the control intervention.

Exercise – both alone and with CPAP – was associated with an increase in maximum heart rate and peak VO2, and decrease in VE/VCO2 slope compared to the CPAP-alone and control groups.

“We found that peak oxygen consumption and muscle performance improved significantly only in the exercise groups, but not with CPAP alone, even though CPAP was most effective in attenuating OSA severity,” wrote Dr. Denise M. Servantes, from the Departamento de Psicobiologia at the Universidade Federal de São Paul in Brazil, and co-authors. “Because peak VO2 is an independent predictor of survival and crucial to the optimal timing of cardiac transplantation, these findings have important clinical implications, even in patients who are adherent to CPAP.”

A significant number of participants in the active intervention groups changed New York Heart Association functional class; the number of patients in the exercise group in class I went from 0%-88% by three months, in the CPAP group it increased from 0% to 47%, and in the CPAP plus exercise group, it increased from 0% to 73%.

The study also found evidence of a trend towards improved sexual function in the participants who undertook both exercise plus CPAP.

All patients in the intervention groups showed improvements in subjective daytime sleepiness and quality of life, although improvements in the Minnesota Living with Heart Failure Questionnaire and Short Form Health Survey (SF-36) were significant only in the two groups that did exercise.

“The data suggest that exercise could be a therapeutic option for patients with HF and OSA who refuse CPAP or are intolerant to it,” the authors wrote. “In this regard, a considerable number of patients with HF and OSA do not experience subjective excessive daytime sleepiness and consequently observe no immediate benefit from using CPAP, which could contribute to poor long-term adherence.”

Individuals in the exercise group showed a slight but significant weight reduction, and those who undertook the exercise program also showed significant improvements in muscle strength and endurance compared to the control group.

The authors commented that another study examining the impact of weight loss program in people with moderate to severe obstructive sleep apnea found weight loss only or combined interventions achieved benefits for C-reactive protein levels, insulin resistance, and serum triglyceride levels. But these benefits weren’t seen with CPAP alone.

“The results of that study, and the present one emphasize the importance of adjunctive therapy of OSA with weight loss and exercise when applicable.”

However they acknowledged that the short duration of the study, and small sample size were limitations, and that this was only a preliminary investigation.

No conflicts of interest were declared.

SOURCE: Servantes D et al. Chest, 2018; 154:808-817. https://doi.org/10.1016/j.chest.2018.05.011. https://journal.chestnet.org/article/S0012-3692(18)30790-6/fulltext

Exercise may be as effective as CPAP in improving obstructive sleep apnea and quality of life in patients with heart failure, according to a study published in the October issue of Chest [https://journal.chestnet.org/article/S0012-3692(18)30790-6/fulltext].

Researchers undertook a randomized, four-arm trial in 65 patients with heart failure and obstructive sleep apnea, which compared the effects of CPAP alone, exercise alone – consisting of three supervised sessions per week for three months, or CPAP plus exercise. A control group received education sessions on the importance of exercise.

The greatest reduction in mean apnea-hypopnea index was seen in the CPAP group, who experienced a mean decrease of 24 events per hour. The exercise plus CPAP group and the exercise only groups showed a mean decrease of 10 events per hour. In contrast, the control group showed no significant decrease in the number of events per hour of sleep.

The authors commented that the change in apnea-hypopnea index was due to reduction in obstructive apneas and hypopneas, and noted the “difficulty of accurately distinguishing obstructive from central hypopneas”.

All the active interventions were associated with significant decreases in arousal index and improvements in sleep-related saturation compared to the control intervention.

Exercise – both alone and with CPAP – was associated with an increase in maximum heart rate and peak VO2, and decrease in VE/VCO2 slope compared to the CPAP-alone and control groups.

“We found that peak oxygen consumption and muscle performance improved significantly only in the exercise groups, but not with CPAP alone, even though CPAP was most effective in attenuating OSA severity,” wrote Dr. Denise M. Servantes, from the Departamento de Psicobiologia at the Universidade Federal de São Paul in Brazil, and co-authors. “Because peak VO2 is an independent predictor of survival and crucial to the optimal timing of cardiac transplantation, these findings have important clinical implications, even in patients who are adherent to CPAP.”

A significant number of participants in the active intervention groups changed New York Heart Association functional class; the number of patients in the exercise group in class I went from 0%-88% by three months, in the CPAP group it increased from 0% to 47%, and in the CPAP plus exercise group, it increased from 0% to 73%.

The study also found evidence of a trend towards improved sexual function in the participants who undertook both exercise plus CPAP.

All patients in the intervention groups showed improvements in subjective daytime sleepiness and quality of life, although improvements in the Minnesota Living with Heart Failure Questionnaire and Short Form Health Survey (SF-36) were significant only in the two groups that did exercise.

“The data suggest that exercise could be a therapeutic option for patients with HF and OSA who refuse CPAP or are intolerant to it,” the authors wrote. “In this regard, a considerable number of patients with HF and OSA do not experience subjective excessive daytime sleepiness and consequently observe no immediate benefit from using CPAP, which could contribute to poor long-term adherence.”

Individuals in the exercise group showed a slight but significant weight reduction, and those who undertook the exercise program also showed significant improvements in muscle strength and endurance compared to the control group.

The authors commented that another study examining the impact of weight loss program in people with moderate to severe obstructive sleep apnea found weight loss only or combined interventions achieved benefits for C-reactive protein levels, insulin resistance, and serum triglyceride levels. But these benefits weren’t seen with CPAP alone.

“The results of that study, and the present one emphasize the importance of adjunctive therapy of OSA with weight loss and exercise when applicable.”

However they acknowledged that the short duration of the study, and small sample size were limitations, and that this was only a preliminary investigation.

No conflicts of interest were declared.

SOURCE: Servantes D et al. Chest, 2018; 154:808-817. https://doi.org/10.1016/j.chest.2018.05.011. https://journal.chestnet.org/article/S0012-3692(18)30790-6/fulltext

In multiple myeloma patients who have no matched donor, haploidentical allogeneic transplantation is feasible and has an acceptable rate of non-relapse mortality in comparison to donor-based transplants, investigators have reported.

The rate of non-relapse mortality at one year was 21% in the retrospective analysis of 96 patients, recently reported in the journal Biology of Blood and Marrow Transplantation.

Haploidentical allogeneic hematopoietic stem cell transplant (allo-HCT) is currently limited in use due to a high rate of relapse, but may hold potential promise for future applications, according to Firoozeh Sahebi, MD, a hematologist with the City of Hope Medical Center, Duarte, Calif., and colleagues. “Our results demonstrate that haploidentical allo-HCT can be safely performed in appropriate patients with MM who lack on HLA-matched sibling or unrelated donor.”

“The allo-HCT platform can be used in the context of other post-transplantation immune-based strategies, such as donor-derived chimeric antigen receptor T cells and natural killer cell infusions, newer immunomodulatory drugs or proteasome inhibitors, bispecific T cell engagers, and bispecific killer cell engagers, to further enhance antitumor effects and ultimately improve survival in an appropriate patient population,” Dr. Sahebi and colleagues said in their report.

The investigators reported results of a retrospective analysis including 96 patients with relapsed multiple myeloma who had failed at least one previous autologous HCT. They underwent haploidentical allo-HCT at European Society for Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Research centers between 2008 and 2016.

Median follow-up in the analysis was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, while 75% had recovery of platelets by day 60, Dr. Sahebi and co-investigators reported.

The 1-year nonrelapse mortality rate was 21%, but the cumulative risk of relapse and progression at 2 years was 56%, according to the study results. Two-year progression-free survival was reported to be 17%, while overall survival was 48%.

Acute graft-versus-host-disease (GVHD) of grades II-IV occurred in 39% by 100 days, while chronic GVHD was seen in 46% at 2 years, the report shows.

Factors linked to improved overall survival at 2 years included use of bone marrow as the source of stem cells, and the use of cyclophosphamide after transplantation, according to Dr. Sahebi and co-authors.

By contrast, factors that had no impact on overall survival, progression-free survival, or non-relapse mortality included disease status (ie, degree of response), gender, conditioning regimen intensity, presence of cytomegalovirus in the blood, or donor-recipient sex mismatch.

This analysis was conducted in part due to the limited availability of matched donors, along with the promising results of allo-HCT in other malignancies, according to investigators.

There were no conflicts of interest to report related to this research, Dr. Sahebi and colleagues reported in the journal.
 

SOURCE: Sahebi F, et al. Biol Blood Marrow Transplant. 2018 Sep 20. pii: S1083-8791(18)30575-5.

In multiple myeloma patients who have no matched donor, haploidentical allogeneic transplantation is feasible and has an acceptable rate of non-relapse mortality in comparison to donor-based transplants, investigators have reported.

The rate of non-relapse mortality at one year was 21% in the retrospective analysis of 96 patients, recently reported in the journal Biology of Blood and Marrow Transplantation.

Haploidentical allogeneic hematopoietic stem cell transplant (allo-HCT) is currently limited in use due to a high rate of relapse, but may hold potential promise for future applications, according to Firoozeh Sahebi, MD, a hematologist with the City of Hope Medical Center, Duarte, Calif., and colleagues. “Our results demonstrate that haploidentical allo-HCT can be safely performed in appropriate patients with MM who lack on HLA-matched sibling or unrelated donor.”

“The allo-HCT platform can be used in the context of other post-transplantation immune-based strategies, such as donor-derived chimeric antigen receptor T cells and natural killer cell infusions, newer immunomodulatory drugs or proteasome inhibitors, bispecific T cell engagers, and bispecific killer cell engagers, to further enhance antitumor effects and ultimately improve survival in an appropriate patient population,” Dr. Sahebi and colleagues said in their report.

The investigators reported results of a retrospective analysis including 96 patients with relapsed multiple myeloma who had failed at least one previous autologous HCT. They underwent haploidentical allo-HCT at European Society for Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Research centers between 2008 and 2016.

Median follow-up in the analysis was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, while 75% had recovery of platelets by day 60, Dr. Sahebi and co-investigators reported.

The 1-year nonrelapse mortality rate was 21%, but the cumulative risk of relapse and progression at 2 years was 56%, according to the study results. Two-year progression-free survival was reported to be 17%, while overall survival was 48%.

Acute graft-versus-host-disease (GVHD) of grades II-IV occurred in 39% by 100 days, while chronic GVHD was seen in 46% at 2 years, the report shows.

Factors linked to improved overall survival at 2 years included use of bone marrow as the source of stem cells, and the use of cyclophosphamide after transplantation, according to Dr. Sahebi and co-authors.

By contrast, factors that had no impact on overall survival, progression-free survival, or non-relapse mortality included disease status (ie, degree of response), gender, conditioning regimen intensity, presence of cytomegalovirus in the blood, or donor-recipient sex mismatch.

This analysis was conducted in part due to the limited availability of matched donors, along with the promising results of allo-HCT in other malignancies, according to investigators.

There were no conflicts of interest to report related to this research, Dr. Sahebi and colleagues reported in the journal.
 

SOURCE: Sahebi F, et al. Biol Blood Marrow Transplant. 2018 Sep 20. pii: S1083-8791(18)30575-5.

In multiple myeloma patients who have no matched donor, haploidentical allogeneic transplantation is feasible and has an acceptable rate of non-relapse mortality in comparison to donor-based transplants, investigators have reported.

The rate of non-relapse mortality at one year was 21% in the retrospective analysis of 96 patients, recently reported in the journal Biology of Blood and Marrow Transplantation.

Haploidentical allogeneic hematopoietic stem cell transplant (allo-HCT) is currently limited in use due to a high rate of relapse, but may hold potential promise for future applications, according to Firoozeh Sahebi, MD, a hematologist with the City of Hope Medical Center, Duarte, Calif., and colleagues. “Our results demonstrate that haploidentical allo-HCT can be safely performed in appropriate patients with MM who lack on HLA-matched sibling or unrelated donor.”

“The allo-HCT platform can be used in the context of other post-transplantation immune-based strategies, such as donor-derived chimeric antigen receptor T cells and natural killer cell infusions, newer immunomodulatory drugs or proteasome inhibitors, bispecific T cell engagers, and bispecific killer cell engagers, to further enhance antitumor effects and ultimately improve survival in an appropriate patient population,” Dr. Sahebi and colleagues said in their report.

The investigators reported results of a retrospective analysis including 96 patients with relapsed multiple myeloma who had failed at least one previous autologous HCT. They underwent haploidentical allo-HCT at European Society for Blood and Marrow Transplantation/Center for International Blood and Marrow Transplant Research centers between 2008 and 2016.

Median follow-up in the analysis was 24 months. Almost all patients (97%) achieved neutrophil engraftment by day 28, while 75% had recovery of platelets by day 60, Dr. Sahebi and co-investigators reported.

The 1-year nonrelapse mortality rate was 21%, but the cumulative risk of relapse and progression at 2 years was 56%, according to the study results. Two-year progression-free survival was reported to be 17%, while overall survival was 48%.

Acute graft-versus-host-disease (GVHD) of grades II-IV occurred in 39% by 100 days, while chronic GVHD was seen in 46% at 2 years, the report shows.

Factors linked to improved overall survival at 2 years included use of bone marrow as the source of stem cells, and the use of cyclophosphamide after transplantation, according to Dr. Sahebi and co-authors.

By contrast, factors that had no impact on overall survival, progression-free survival, or non-relapse mortality included disease status (ie, degree of response), gender, conditioning regimen intensity, presence of cytomegalovirus in the blood, or donor-recipient sex mismatch.

This analysis was conducted in part due to the limited availability of matched donors, along with the promising results of allo-HCT in other malignancies, according to investigators.

There were no conflicts of interest to report related to this research, Dr. Sahebi and colleagues reported in the journal.
 

SOURCE: Sahebi F, et al. Biol Blood Marrow Transplant. 2018 Sep 20. pii: S1083-8791(18)30575-5.

Antibiotics prescribed within the first 2 years of life are associated with the development of early childhood obesity, results of a large, retrospective study suggest.

Acid-suppressing medications were also associated with childhood obesity, although to a lesser extent, according to results of the study, which included more than a quarter of a million children receiving care in the U.S. military health system.

Antibiotics and antacids are both microbiota-altering medications, researchers said, noting that obesity has been linked to variations in the native gut microbiota.

While the evidence from previous studies is conflicting on whether microbiota-altering medications may play a role in development of childhood obesity, this study does suggest such medications may lead to weight gain early in life, they said in the journal Gut.

“Providers should practice appropriate stewardship as the first-line response to these findings,” said Christopher M. Stark, MD, of the William Beaumont Army Medical Center, El Paso, Tex., and his co-authors.

This retrospective analysis included the largest cohort of pediatric patients ever studied for the link between antibiotics and obesity, according to Dr. Stark and colleagues, and was the first to look at the link between acid-suppressing medications and obesity in that age group.

The analysis included a total of 333,353 U.S. Department of Defense TRICARE beneficiaries born between October 2006 and September 2013 who were exposed to antibiotics, histamine-2-receptor antagonists (H2RAs), or proton pump inhibitors (PPIs) within the first 2 years of life.

Patients were followed past their initial exposure period, up to 8 years of age in some cases, investigators said.

Antibiotics were prescribed in 72.4% of those children, while H2RAs and PPIs were prescribed in 11.8% and 3.3%, respectively, with a substantial number of children receiving more than one of the medications of interest for this study.

A total of 46,993 (14.1%) of the children developed obesity. Of those obese children only 9,268, or 11%, had no antibiotic or acid suppressant prescriptions on record in the first 2 years of life, the reported data show.

Antibiotic prescriptions were associated with a 26% increase in obesity risk (unadjusted hazard ratio, 1.26; 95% CI, 1.23-1.28), investigators reported. That association strengthened steadily with the number of antibiotic prescriptions, with adjusted hazard ratios of 1.12 (95% CI, 1.09-1.15) for a single prescription, up to 1.42 (95% CI, 1.37-1.46) for 4 or more prescriptions

Likewise, H2RAs and PPIs were associated, albeit weakly, with an increased hazard of obesity, investigators said. The adjusted hazard ratios and 95% confidence intervals were 1.02 (1.01-1.03) for PPIs and 1.01 (1.004-1.02) for H2RA prescriptions.

The risk of obesity steadily climbed for those receiving multiple medications, researchers added, from a hazard ratio of 1.21 for one medication, 1.31 for two, and 1.42 for three, data show.

Dr. Stark and co-authors declared no competing interests related to the study.

SOURCE: Stark CM, et al. Gut. 2018 Oct 30. pii: gutjnl-2017-314971.

Antibiotics prescribed within the first 2 years of life are associated with the development of early childhood obesity, results of a large, retrospective study suggest.

Acid-suppressing medications were also associated with childhood obesity, although to a lesser extent, according to results of the study, which included more than a quarter of a million children receiving care in the U.S. military health system.

Antibiotics and antacids are both microbiota-altering medications, researchers said, noting that obesity has been linked to variations in the native gut microbiota.

While the evidence from previous studies is conflicting on whether microbiota-altering medications may play a role in development of childhood obesity, this study does suggest such medications may lead to weight gain early in life, they said in the journal Gut.

“Providers should practice appropriate stewardship as the first-line response to these findings,” said Christopher M. Stark, MD, of the William Beaumont Army Medical Center, El Paso, Tex., and his co-authors.

This retrospective analysis included the largest cohort of pediatric patients ever studied for the link between antibiotics and obesity, according to Dr. Stark and colleagues, and was the first to look at the link between acid-suppressing medications and obesity in that age group.

The analysis included a total of 333,353 U.S. Department of Defense TRICARE beneficiaries born between October 2006 and September 2013 who were exposed to antibiotics, histamine-2-receptor antagonists (H2RAs), or proton pump inhibitors (PPIs) within the first 2 years of life.

Patients were followed past their initial exposure period, up to 8 years of age in some cases, investigators said.

Antibiotics were prescribed in 72.4% of those children, while H2RAs and PPIs were prescribed in 11.8% and 3.3%, respectively, with a substantial number of children receiving more than one of the medications of interest for this study.

A total of 46,993 (14.1%) of the children developed obesity. Of those obese children only 9,268, or 11%, had no antibiotic or acid suppressant prescriptions on record in the first 2 years of life, the reported data show.

Antibiotic prescriptions were associated with a 26% increase in obesity risk (unadjusted hazard ratio, 1.26; 95% CI, 1.23-1.28), investigators reported. That association strengthened steadily with the number of antibiotic prescriptions, with adjusted hazard ratios of 1.12 (95% CI, 1.09-1.15) for a single prescription, up to 1.42 (95% CI, 1.37-1.46) for 4 or more prescriptions

Likewise, H2RAs and PPIs were associated, albeit weakly, with an increased hazard of obesity, investigators said. The adjusted hazard ratios and 95% confidence intervals were 1.02 (1.01-1.03) for PPIs and 1.01 (1.004-1.02) for H2RA prescriptions.

The risk of obesity steadily climbed for those receiving multiple medications, researchers added, from a hazard ratio of 1.21 for one medication, 1.31 for two, and 1.42 for three, data show.

Dr. Stark and co-authors declared no competing interests related to the study.

SOURCE: Stark CM, et al. Gut. 2018 Oct 30. pii: gutjnl-2017-314971.

Antibiotics prescribed within the first 2 years of life are associated with the development of early childhood obesity, results of a large, retrospective study suggest.

Acid-suppressing medications were also associated with childhood obesity, although to a lesser extent, according to results of the study, which included more than a quarter of a million children receiving care in the U.S. military health system.

Antibiotics and antacids are both microbiota-altering medications, researchers said, noting that obesity has been linked to variations in the native gut microbiota.

While the evidence from previous studies is conflicting on whether microbiota-altering medications may play a role in development of childhood obesity, this study does suggest such medications may lead to weight gain early in life, they said in the journal Gut.

“Providers should practice appropriate stewardship as the first-line response to these findings,” said Christopher M. Stark, MD, of the William Beaumont Army Medical Center, El Paso, Tex., and his co-authors.

This retrospective analysis included the largest cohort of pediatric patients ever studied for the link between antibiotics and obesity, according to Dr. Stark and colleagues, and was the first to look at the link between acid-suppressing medications and obesity in that age group.

The analysis included a total of 333,353 U.S. Department of Defense TRICARE beneficiaries born between October 2006 and September 2013 who were exposed to antibiotics, histamine-2-receptor antagonists (H2RAs), or proton pump inhibitors (PPIs) within the first 2 years of life.

Patients were followed past their initial exposure period, up to 8 years of age in some cases, investigators said.

Antibiotics were prescribed in 72.4% of those children, while H2RAs and PPIs were prescribed in 11.8% and 3.3%, respectively, with a substantial number of children receiving more than one of the medications of interest for this study.

A total of 46,993 (14.1%) of the children developed obesity. Of those obese children only 9,268, or 11%, had no antibiotic or acid suppressant prescriptions on record in the first 2 years of life, the reported data show.

Antibiotic prescriptions were associated with a 26% increase in obesity risk (unadjusted hazard ratio, 1.26; 95% CI, 1.23-1.28), investigators reported. That association strengthened steadily with the number of antibiotic prescriptions, with adjusted hazard ratios of 1.12 (95% CI, 1.09-1.15) for a single prescription, up to 1.42 (95% CI, 1.37-1.46) for 4 or more prescriptions

Likewise, H2RAs and PPIs were associated, albeit weakly, with an increased hazard of obesity, investigators said. The adjusted hazard ratios and 95% confidence intervals were 1.02 (1.01-1.03) for PPIs and 1.01 (1.004-1.02) for H2RA prescriptions.

The risk of obesity steadily climbed for those receiving multiple medications, researchers added, from a hazard ratio of 1.21 for one medication, 1.31 for two, and 1.42 for three, data show.

Dr. Stark and co-authors declared no competing interests related to the study.

SOURCE: Stark CM, et al. Gut. 2018 Oct 30. pii: gutjnl-2017-314971.

CHICAGO – Women who self-reported a high level of physical and emotional abuse as children had a nearly three-fold increased incidence of systemic lupus erythematosus during adulthood, in a study of more than 67,000 American nurses.

The results also suggested that development of depression and post-traumatic stress disorder (PTSD) may have been intermediary steps between episodes of childhood abuse and later development of systemic lupus erythematosus (SLE), Candace H. Feldman, MD, said at the annual meeting of the American College of Rheumatology.

These findings suggest the “importance of screening for childhood abuse exposures as well as for depression and PTSD in routine practice,” although Dr. Feldman acknowledged that interventions aimed at treating depression and PTSD have as of now no proven role for mitigating SLE.

The analysis Dr. Feldman and her associates ran on data collected in the Nurses Health Study II also documented a “striking” number of the enrolled women who completed the survey in 2001 and reported a history of abuse when they were 11 years old or younger: 30% of the 67,516 respondents reported a moderate level of abuse, and 24% reported a high level of abuse. An additional 22% reported either no or a very low level of abuse. These numbers suggest that abuse of girls “is very common and probably underreported,” she said in a video interview.

The Nurses Health Study II enrolled more than 116,429 U.S. women in 1989 who were 25-42 years old and had no history of SLE. Recording of incident SLE cases began in 1991 and for this analysis continued for 24 years, through 2015, during which time 94 women developed SLE that was confirmed in a review by two rheumatologists applying the 1997 SLE classification criteria (Arthritis Rheum. 1997 Sept;40[9]:1725. The incidence of SLE was 2.57-fold more common among women who reported a high level of abuse, compared with those who had no or very low abuse, after adjustment for several demographic and clinical confounders, reported Dr. Feldman, a rheumatologist at Brigham and Women’s Hospital in Boston.

“To our knowledge this is the first study to prospectively look at exposure to different forms of childhood abuse and SLE incidence in a general population of women,” she said.

To make the analysis more prospective the researchers also ran a calculation that considered only SLE cases that appeared after completion of the 2001 abuse survey. Using this criterion the incidence was 3.11-fold higher among women who reported a high level of childhood abuse. Further analyses showed that statistically a diagnosis of PTSD accounted for about 23% of the risk for developing SLE, and depression appeared responsible for about 17% of the risk. The analysis also showed no statistically significant link between sexual abuse in childhood or as a teenager and later onset of SLE.

The findings are consistent with prior reports that linked stress to development of various autoimmune diseases, Dr. Feldman noted. She speculated that high childhood stress could cause changes in inflammation, immune function, epigenetics, the autonomic nervous system, and endocrine pathways that could play a role in triggering depression or PTSD, and eventually SLE.
 

[email protected]

On Twitter @mitchelzoler

SOURCE:Feldman C et al. Arthritis Rheumatol. 2018;70(suppl 10) Abstract 2807.

CHICAGO – Women who self-reported a high level of physical and emotional abuse as children had a nearly three-fold increased incidence of systemic lupus erythematosus during adulthood, in a study of more than 67,000 American nurses.

The results also suggested that development of depression and post-traumatic stress disorder (PTSD) may have been intermediary steps between episodes of childhood abuse and later development of systemic lupus erythematosus (SLE), Candace H. Feldman, MD, said at the annual meeting of the American College of Rheumatology.

These findings suggest the “importance of screening for childhood abuse exposures as well as for depression and PTSD in routine practice,” although Dr. Feldman acknowledged that interventions aimed at treating depression and PTSD have as of now no proven role for mitigating SLE.

The analysis Dr. Feldman and her associates ran on data collected in the Nurses Health Study II also documented a “striking” number of the enrolled women who completed the survey in 2001 and reported a history of abuse when they were 11 years old or younger: 30% of the 67,516 respondents reported a moderate level of abuse, and 24% reported a high level of abuse. An additional 22% reported either no or a very low level of abuse. These numbers suggest that abuse of girls “is very common and probably underreported,” she said in a video interview.

The Nurses Health Study II enrolled more than 116,429 U.S. women in 1989 who were 25-42 years old and had no history of SLE. Recording of incident SLE cases began in 1991 and for this analysis continued for 24 years, through 2015, during which time 94 women developed SLE that was confirmed in a review by two rheumatologists applying the 1997 SLE classification criteria (Arthritis Rheum. 1997 Sept;40[9]:1725. The incidence of SLE was 2.57-fold more common among women who reported a high level of abuse, compared with those who had no or very low abuse, after adjustment for several demographic and clinical confounders, reported Dr. Feldman, a rheumatologist at Brigham and Women’s Hospital in Boston.

“To our knowledge this is the first study to prospectively look at exposure to different forms of childhood abuse and SLE incidence in a general population of women,” she said.

To make the analysis more prospective the researchers also ran a calculation that considered only SLE cases that appeared after completion of the 2001 abuse survey. Using this criterion the incidence was 3.11-fold higher among women who reported a high level of childhood abuse. Further analyses showed that statistically a diagnosis of PTSD accounted for about 23% of the risk for developing SLE, and depression appeared responsible for about 17% of the risk. The analysis also showed no statistically significant link between sexual abuse in childhood or as a teenager and later onset of SLE.

The findings are consistent with prior reports that linked stress to development of various autoimmune diseases, Dr. Feldman noted. She speculated that high childhood stress could cause changes in inflammation, immune function, epigenetics, the autonomic nervous system, and endocrine pathways that could play a role in triggering depression or PTSD, and eventually SLE.
 

[email protected]

On Twitter @mitchelzoler

SOURCE:Feldman C et al. Arthritis Rheumatol. 2018;70(suppl 10) Abstract 2807.

CHICAGO – Women who self-reported a high level of physical and emotional abuse as children had a nearly three-fold increased incidence of systemic lupus erythematosus during adulthood, in a study of more than 67,000 American nurses.

The results also suggested that development of depression and post-traumatic stress disorder (PTSD) may have been intermediary steps between episodes of childhood abuse and later development of systemic lupus erythematosus (SLE), Candace H. Feldman, MD, said at the annual meeting of the American College of Rheumatology.

These findings suggest the “importance of screening for childhood abuse exposures as well as for depression and PTSD in routine practice,” although Dr. Feldman acknowledged that interventions aimed at treating depression and PTSD have as of now no proven role for mitigating SLE.

The analysis Dr. Feldman and her associates ran on data collected in the Nurses Health Study II also documented a “striking” number of the enrolled women who completed the survey in 2001 and reported a history of abuse when they were 11 years old or younger: 30% of the 67,516 respondents reported a moderate level of abuse, and 24% reported a high level of abuse. An additional 22% reported either no or a very low level of abuse. These numbers suggest that abuse of girls “is very common and probably underreported,” she said in a video interview.

The Nurses Health Study II enrolled more than 116,429 U.S. women in 1989 who were 25-42 years old and had no history of SLE. Recording of incident SLE cases began in 1991 and for this analysis continued for 24 years, through 2015, during which time 94 women developed SLE that was confirmed in a review by two rheumatologists applying the 1997 SLE classification criteria (Arthritis Rheum. 1997 Sept;40[9]:1725. The incidence of SLE was 2.57-fold more common among women who reported a high level of abuse, compared with those who had no or very low abuse, after adjustment for several demographic and clinical confounders, reported Dr. Feldman, a rheumatologist at Brigham and Women’s Hospital in Boston.

“To our knowledge this is the first study to prospectively look at exposure to different forms of childhood abuse and SLE incidence in a general population of women,” she said.

To make the analysis more prospective the researchers also ran a calculation that considered only SLE cases that appeared after completion of the 2001 abuse survey. Using this criterion the incidence was 3.11-fold higher among women who reported a high level of childhood abuse. Further analyses showed that statistically a diagnosis of PTSD accounted for about 23% of the risk for developing SLE, and depression appeared responsible for about 17% of the risk. The analysis also showed no statistically significant link between sexual abuse in childhood or as a teenager and later onset of SLE.

The findings are consistent with prior reports that linked stress to development of various autoimmune diseases, Dr. Feldman noted. She speculated that high childhood stress could cause changes in inflammation, immune function, epigenetics, the autonomic nervous system, and endocrine pathways that could play a role in triggering depression or PTSD, and eventually SLE.
 

[email protected]

On Twitter @mitchelzoler

SOURCE:Feldman C et al. Arthritis Rheumatol. 2018;70(suppl 10) Abstract 2807.

Photo by Cristina Granados

The U.S. Food and Drug Administration (FDA) has granted breakthrough device designation for pathogen-reduced cryoprecipitate manufactured from plasma treated with the INTERCEPT Blood System.

Cerus Corporation aims to seek FDA approval for this pathogen-reduced cryoprecipitate to treat massive hemorrhage.

“The proposed label indication for pathogen-reduced cryoprecipitate would be to control massive bleeding associated with fibrinogen deficiency,” said Laurence Corash, chief scientific officer of Cerus.

The proposed shelf life for pathogen-reduced cyroprecipitate is 5 days at room temperature.

The INTERCEPT Blood System is already FDA-approved for the inactivation of pathogens in platelets and plasma.

“Cryo[precipitate] is a natural extension to our current FDA-approved INTERCEPT Blood System for plasma,” said William “Obi” Greenman, president and chief executive officer of Cerus.

If the FDA granted approval, INTERCEPT-treated plasma could be manufactured into pathogen-reduced cryoprecipitate.

About breakthrough device designation

The FDA says it grants breakthrough designation to devices “that provide more effective treatment or diagnosis of life-threatening or irreversibly debilitating human diseases or conditions.”

Breakthrough designation is intended to expedite the development, assessment, and review of medical devices. The breakthrough devices program supersedes the FDA’s expedited access pathway and priority review programs.

Photo by Cristina Granados

The U.S. Food and Drug Administration (FDA) has granted breakthrough device designation for pathogen-reduced cryoprecipitate manufactured from plasma treated with the INTERCEPT Blood System.

Cerus Corporation aims to seek FDA approval for this pathogen-reduced cryoprecipitate to treat massive hemorrhage.

“The proposed label indication for pathogen-reduced cryoprecipitate would be to control massive bleeding associated with fibrinogen deficiency,” said Laurence Corash, chief scientific officer of Cerus.

The proposed shelf life for pathogen-reduced cyroprecipitate is 5 days at room temperature.

The INTERCEPT Blood System is already FDA-approved for the inactivation of pathogens in platelets and plasma.

“Cryo[precipitate] is a natural extension to our current FDA-approved INTERCEPT Blood System for plasma,” said William “Obi” Greenman, president and chief executive officer of Cerus.

If the FDA granted approval, INTERCEPT-treated plasma could be manufactured into pathogen-reduced cryoprecipitate.

About breakthrough device designation

The FDA says it grants breakthrough designation to devices “that provide more effective treatment or diagnosis of life-threatening or irreversibly debilitating human diseases or conditions.”

Breakthrough designation is intended to expedite the development, assessment, and review of medical devices. The breakthrough devices program supersedes the FDA’s expedited access pathway and priority review programs.

Photo by Cristina Granados

The U.S. Food and Drug Administration (FDA) has granted breakthrough device designation for pathogen-reduced cryoprecipitate manufactured from plasma treated with the INTERCEPT Blood System.

Cerus Corporation aims to seek FDA approval for this pathogen-reduced cryoprecipitate to treat massive hemorrhage.

“The proposed label indication for pathogen-reduced cryoprecipitate would be to control massive bleeding associated with fibrinogen deficiency,” said Laurence Corash, chief scientific officer of Cerus.

The proposed shelf life for pathogen-reduced cyroprecipitate is 5 days at room temperature.

The INTERCEPT Blood System is already FDA-approved for the inactivation of pathogens in platelets and plasma.

“Cryo[precipitate] is a natural extension to our current FDA-approved INTERCEPT Blood System for plasma,” said William “Obi” Greenman, president and chief executive officer of Cerus.

If the FDA granted approval, INTERCEPT-treated plasma could be manufactured into pathogen-reduced cryoprecipitate.

About breakthrough device designation

The FDA says it grants breakthrough designation to devices “that provide more effective treatment or diagnosis of life-threatening or irreversibly debilitating human diseases or conditions.”

Breakthrough designation is intended to expedite the development, assessment, and review of medical devices. The breakthrough devices program supersedes the FDA’s expedited access pathway and priority review programs.

A joint panel of the Food and Drug Administration voted Nov. 2 in support of brexanolone infusion as a treatment for postpartum depression.

The 17-1 vote by members of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was based primarily on data from three studies, including 247 women aged 18-44 years with postpartum depression; 140 received brexanolone and 107 received placebo. Effectiveness was assessed based on the Hamilton Depression Scale (HAM-D) at the end of the infusion (hour 60).

In all three studies, patients given brexanolone showed significantly improved HAM-D scores, compared with placebo. The patients experienced significant differences at hour 24, which illustrated the rapid response. “The individual item scores of the HAM-D consistently favored brexanolone IV over placebo, confirming an overall antidepressant effect of the drug,” according to the briefing document of Sage Therapeutics, developer of the drug. In addition, more than 80% of the patients in the treatment and placebo groups sustained their improvement in symptoms at 30 days after the end of the infusion.

“[Postpartum depression] is symptomatically indistinguishable from an episode of major depression,” the FDA briefing document said. “However, the timing of its onset has led to its recognition as a potentially unique illness. There are no drugs specifically approved to treat [postpartum depression].”

Some clinicians use drugs approved for major depression to treat postpartum depression, but the effectiveness of these drugs is limited, the agency said. Other interventions, such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and psychotherapy also are used, but they can take several weeks to show results.

Recent estimates of postpartum depression in the United States range from about 8% to 20%, according to the FDA document. and both the FDA and Sage Therapeutics agreed on the need for additional treatment options for women with postpartum depression. Potential advantages of brexanolone include a rapid onset of action and significant improvement of depressive symptoms, according to Sage.

The treatment protocol for brexanolone involves a single 60-hour continuous infusion with a recommended maximum dose of 90 µg/kg/h, referred to as a “90 dose regimen.” The patient receives a single infusion per episode of postpartum depression. The infusion includes three dosing phases: titration at 30 μg/kg/h for 4 hours followed by 60 μg/kg/h for 20 hours (hour 0-24), maintenance at 90 μg/kg/h for 28 hours (hour 24-52), and taper at 60 μg/kg/h for 4 hours – followed by 30 μg/kg/h for 4 hours (hour 52-60).

Brexanolone is an allosteric modulator of GABAA receptors and “a new molecular entity not currently marketed anywhere in the world for any indication,” according to the FDA document. The drug originally was studied as a treatment for seizure patients before its antidepressant properties were discovered.

Adverse reactions observed in 3% or more of the brexanolone patients during the 60-hour treatment and 4-week follow-up included dry mouth, infusion site pain, fatigue, headache, sedation/somnolence, dizziness/vertigo, and loss of consciousness.

Of those reactions, loss of consciousness was the issue of greatest concern to the committee members and informed their discussion of the strict Risk Evaluation and Mitigation Strategy protocol that would be needed to accompany approval of the drug. The details of the REMS will be determined, but the basics of the FDA’s proposed REMS to mitigate the risk of loss of consciousness include administration of the drug only in medically supervised settings by an authorized representative.

In addition, the proposed REMS states that the authorized representative must “establish policies and procedures to ensure that 1) all staff are trained on the risks and 2) the product is not dispensed for use outside the health care setting.”

The proposed REMS also stated that, “Patients must be continuously monitored for the duration of the infusion and 12 hours after, by health care provider who can intervene if the patient experiences excessive sedation or loss of consciousness.”

Despite those concerns, which most committee members thought could be addressed by the REMS, the overall impression of the committees’ members was that brexanolone could have a significant impact on postpartum depression. According to one member, brexanolone is mechanistically “groundbreaking” and “could be a tremendous help in changing the trajectory of postpartum depression.”

The FDA usually follows its panels’ recommendations, which are not binding.

A joint panel of the Food and Drug Administration voted Nov. 2 in support of brexanolone infusion as a treatment for postpartum depression.

The 17-1 vote by members of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was based primarily on data from three studies, including 247 women aged 18-44 years with postpartum depression; 140 received brexanolone and 107 received placebo. Effectiveness was assessed based on the Hamilton Depression Scale (HAM-D) at the end of the infusion (hour 60).

In all three studies, patients given brexanolone showed significantly improved HAM-D scores, compared with placebo. The patients experienced significant differences at hour 24, which illustrated the rapid response. “The individual item scores of the HAM-D consistently favored brexanolone IV over placebo, confirming an overall antidepressant effect of the drug,” according to the briefing document of Sage Therapeutics, developer of the drug. In addition, more than 80% of the patients in the treatment and placebo groups sustained their improvement in symptoms at 30 days after the end of the infusion.

“[Postpartum depression] is symptomatically indistinguishable from an episode of major depression,” the FDA briefing document said. “However, the timing of its onset has led to its recognition as a potentially unique illness. There are no drugs specifically approved to treat [postpartum depression].”

Some clinicians use drugs approved for major depression to treat postpartum depression, but the effectiveness of these drugs is limited, the agency said. Other interventions, such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and psychotherapy also are used, but they can take several weeks to show results.

Recent estimates of postpartum depression in the United States range from about 8% to 20%, according to the FDA document. and both the FDA and Sage Therapeutics agreed on the need for additional treatment options for women with postpartum depression. Potential advantages of brexanolone include a rapid onset of action and significant improvement of depressive symptoms, according to Sage.

The treatment protocol for brexanolone involves a single 60-hour continuous infusion with a recommended maximum dose of 90 µg/kg/h, referred to as a “90 dose regimen.” The patient receives a single infusion per episode of postpartum depression. The infusion includes three dosing phases: titration at 30 μg/kg/h for 4 hours followed by 60 μg/kg/h for 20 hours (hour 0-24), maintenance at 90 μg/kg/h for 28 hours (hour 24-52), and taper at 60 μg/kg/h for 4 hours – followed by 30 μg/kg/h for 4 hours (hour 52-60).

Brexanolone is an allosteric modulator of GABAA receptors and “a new molecular entity not currently marketed anywhere in the world for any indication,” according to the FDA document. The drug originally was studied as a treatment for seizure patients before its antidepressant properties were discovered.

Adverse reactions observed in 3% or more of the brexanolone patients during the 60-hour treatment and 4-week follow-up included dry mouth, infusion site pain, fatigue, headache, sedation/somnolence, dizziness/vertigo, and loss of consciousness.

Of those reactions, loss of consciousness was the issue of greatest concern to the committee members and informed their discussion of the strict Risk Evaluation and Mitigation Strategy protocol that would be needed to accompany approval of the drug. The details of the REMS will be determined, but the basics of the FDA’s proposed REMS to mitigate the risk of loss of consciousness include administration of the drug only in medically supervised settings by an authorized representative.

In addition, the proposed REMS states that the authorized representative must “establish policies and procedures to ensure that 1) all staff are trained on the risks and 2) the product is not dispensed for use outside the health care setting.”

The proposed REMS also stated that, “Patients must be continuously monitored for the duration of the infusion and 12 hours after, by health care provider who can intervene if the patient experiences excessive sedation or loss of consciousness.”

Despite those concerns, which most committee members thought could be addressed by the REMS, the overall impression of the committees’ members was that brexanolone could have a significant impact on postpartum depression. According to one member, brexanolone is mechanistically “groundbreaking” and “could be a tremendous help in changing the trajectory of postpartum depression.”

The FDA usually follows its panels’ recommendations, which are not binding.

A joint panel of the Food and Drug Administration voted Nov. 2 in support of brexanolone infusion as a treatment for postpartum depression.

The 17-1 vote by members of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was based primarily on data from three studies, including 247 women aged 18-44 years with postpartum depression; 140 received brexanolone and 107 received placebo. Effectiveness was assessed based on the Hamilton Depression Scale (HAM-D) at the end of the infusion (hour 60).

In all three studies, patients given brexanolone showed significantly improved HAM-D scores, compared with placebo. The patients experienced significant differences at hour 24, which illustrated the rapid response. “The individual item scores of the HAM-D consistently favored brexanolone IV over placebo, confirming an overall antidepressant effect of the drug,” according to the briefing document of Sage Therapeutics, developer of the drug. In addition, more than 80% of the patients in the treatment and placebo groups sustained their improvement in symptoms at 30 days after the end of the infusion.

“[Postpartum depression] is symptomatically indistinguishable from an episode of major depression,” the FDA briefing document said. “However, the timing of its onset has led to its recognition as a potentially unique illness. There are no drugs specifically approved to treat [postpartum depression].”

Some clinicians use drugs approved for major depression to treat postpartum depression, but the effectiveness of these drugs is limited, the agency said. Other interventions, such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and psychotherapy also are used, but they can take several weeks to show results.

Recent estimates of postpartum depression in the United States range from about 8% to 20%, according to the FDA document. and both the FDA and Sage Therapeutics agreed on the need for additional treatment options for women with postpartum depression. Potential advantages of brexanolone include a rapid onset of action and significant improvement of depressive symptoms, according to Sage.

The treatment protocol for brexanolone involves a single 60-hour continuous infusion with a recommended maximum dose of 90 µg/kg/h, referred to as a “90 dose regimen.” The patient receives a single infusion per episode of postpartum depression. The infusion includes three dosing phases: titration at 30 μg/kg/h for 4 hours followed by 60 μg/kg/h for 20 hours (hour 0-24), maintenance at 90 μg/kg/h for 28 hours (hour 24-52), and taper at 60 μg/kg/h for 4 hours – followed by 30 μg/kg/h for 4 hours (hour 52-60).

Brexanolone is an allosteric modulator of GABAA receptors and “a new molecular entity not currently marketed anywhere in the world for any indication,” according to the FDA document. The drug originally was studied as a treatment for seizure patients before its antidepressant properties were discovered.

Adverse reactions observed in 3% or more of the brexanolone patients during the 60-hour treatment and 4-week follow-up included dry mouth, infusion site pain, fatigue, headache, sedation/somnolence, dizziness/vertigo, and loss of consciousness.

Of those reactions, loss of consciousness was the issue of greatest concern to the committee members and informed their discussion of the strict Risk Evaluation and Mitigation Strategy protocol that would be needed to accompany approval of the drug. The details of the REMS will be determined, but the basics of the FDA’s proposed REMS to mitigate the risk of loss of consciousness include administration of the drug only in medically supervised settings by an authorized representative.

In addition, the proposed REMS states that the authorized representative must “establish policies and procedures to ensure that 1) all staff are trained on the risks and 2) the product is not dispensed for use outside the health care setting.”

The proposed REMS also stated that, “Patients must be continuously monitored for the duration of the infusion and 12 hours after, by health care provider who can intervene if the patient experiences excessive sedation or loss of consciousness.”

Despite those concerns, which most committee members thought could be addressed by the REMS, the overall impression of the committees’ members was that brexanolone could have a significant impact on postpartum depression. According to one member, brexanolone is mechanistically “groundbreaking” and “could be a tremendous help in changing the trajectory of postpartum depression.”

The FDA usually follows its panels’ recommendations, which are not binding.